G2Cdb::Gene report

Gene id
G00000973
Gene symbol
Tpi1 (MGI)
Species
Mus musculus
Description
triosephosphate isomerase 1
Orthologue
G00002222 (Homo sapiens)

Databases (9)

Curated Gene
OTTMUSG00000017534 (Vega mouse gene)
Gene
ENSMUSG00000023456 (Ensembl mouse gene)
21991 (Entrez Gene)
139 (G2Cdb plasticity & disease)
Gene Expression
NM_009415 (Allen Brain Atlas)
21991 (Genepaint)
Literature
190450 (OMIM)
Marker Symbol
MGI:98797 (MGI)
Protein Sequence
P17751 (UniProt)

Synonyms (1)

  • Tpi-1

Literature (45)

Pubmed - other

  • A high-resolution anatomical atlas of the transcriptome in the mouse embryo.

    Diez-Roux G, Banfi S, Sultan M, Geffers L, Anand S, Rozado D, Magen A, Canidio E, Pagani M, Peluso I, Lin-Marq N, Koch M, Bilio M, Cantiello I, Verde R, De Masi C, Bianchi SA, Cicchini J, Perroud E, Mehmeti S, Dagand E, Schrinner S, Nürnberger A, Schmidt K, Metz K, Zwingmann C, Brieske N, Springer C, Hernandez AM, Herzog S, Grabbe F, Sieverding C, Fischer B, Schrader K, Brockmeyer M, Dettmer S, Helbig C, Alunni V, Battaini MA, Mura C, Henrichsen CN, Garcia-Lopez R, Echevarria D, Puelles E, Garcia-Calero E, Kruse S, Uhr M, Kauck C, Feng G, Milyaev N, Ong CK, Kumar L, Lam M, Semple CA, Gyenesei A, Mundlos S, Radelof U, Lehrach H, Sarmientos P, Reymond A, Davidson DR, Dollé P, Antonarakis SE, Yaspo ML, Martinez S, Baldock RA, Eichele G and Ballabio A

    Telethon Institute of Genetics and Medicine, Naples, Italy.

    Ascertaining when and where genes are expressed is of crucial importance to understanding or predicting the physiological role of genes and proteins and how they interact to form the complex networks that underlie organ development and function. It is, therefore, crucial to determine on a genome-wide level, the spatio-temporal gene expression profiles at cellular resolution. This information is provided by colorimetric RNA in situ hybridization that can elucidate expression of genes in their native context and does so at cellular resolution. We generated what is to our knowledge the first genome-wide transcriptome atlas by RNA in situ hybridization of an entire mammalian organism, the developing mouse at embryonic day 14.5. This digital transcriptome atlas, the Eurexpress atlas (http://www.eurexpress.org), consists of a searchable database of annotated images that can be interactively viewed. We generated anatomy-based expression profiles for over 18,000 coding genes and over 400 microRNAs. We identified 1,002 tissue-specific genes that are a source of novel tissue-specific markers for 37 different anatomical structures. The quality and the resolution of the data revealed novel molecular domains for several developing structures, such as the telencephalon, a novel organization for the hypothalamus, and insight on the Wnt network involved in renal epithelial differentiation during kidney development. The digital transcriptome atlas is a powerful resource to determine co-expression of genes, to identify cell populations and lineages, and to identify functional associations between genes relevant to development and disease.

    Funded by: Medical Research Council: MC_U127527203; Telethon: TGM11S03

    PLoS biology 2011;9;1;e1000582

  • Effects of Tau on the activity of triose phosphate isomerase (TPI) in brain cells.

    Park SA, Park HW, Kim NH, Kim YH, Kwak MJ, Shin JS and Kim CW

    School of Life Sciences and Biotechnology, Korea University, 1, 5-ga Anam-dong, Sungbuk-ku, Seoul 136-701, Republic of Korea.

    Tau is a main component of the aberrant paired helical filaments (PHF) found in Alzheimer's disease (AD). It has also been reported to enhance oxidative stress, which is a major factor in the pathogenesis of neurodegenerative diseases. However, protective functions of Tau have recently been reported, including antagonizing apoptosis, in addition to its role in stabilizing microtubules. In this study, the interaction between Tau and triose phosphate isomerase (TPI) in a normal, nondisease state as well as in a neurodegeneration state was examined and demonstrated for the first time. More importantly, we also showed that Tau protects TPI against oxidative damage. An oxidative stress-induced decrease in the activity of TPI was attenuated in Tau-overexpressing cells, indicating that Tau protects TPI against oxidative damage. By contrast, the activity of TPI was decreased in Tau-transgenic (Tg) mice compared to non-Tg (NTg) mice even though protein levels were not changed in both groups. Some TPIs were found on the PHF in Tg mice, which explains the decrease in the activity of TPI. Taken together, we concluded that while Tau binds and protects TPI in normal cells, and conversely, the formation of PHF induced by Tau phosphorylation trap some TPI and trigger the functional loss of TPI in the development of neurodegenerative diseases. Our results provide new insights into understanding the in-depth involvement of Tau in the development of neurodegenerative disorders.

    Neurochemistry international 2010;56;8;886-92

  • Hearts of hypoxia-inducible factor prolyl 4-hydroxylase-2 hypomorphic mice show protection against acute ischemia-reperfusion injury.

    Hyvärinen J, Hassinen IE, Sormunen R, Mäki JM, Kivirikko KI, Koivunen P and Myllyharju J

    Oulu Center for Cell-Matrix Research, and Department of Medical Biochemistry and Molecular Biology, University of Oulu, FIN-90014 Oulu, Finland.

    Hypoxia-inducible factor (HIF) has a pivotal role in oxygen homeostasis and cardioprotection mediated by ischemic preconditioning. Its stability is regulated by HIF prolyl 4-hydroxylases (HIF-P4Hs), the inhibition of which is regarded as a promising strategy for treating diseases such as anemia and ischemia. We generated a viable Hif-p4h-2 hypomorph mouse line (Hif-p4h-2(gt/gt)) that expresses decreased amounts of wild-type Hif-p4h-2 mRNA: 8% in the heart; 15% in the skeletal muscle; 34-47% in the kidney, spleen, lung, and bladder; 60% in the brain; and 85% in the liver. These mice have no polycythemia and show no signs of the dilated cardiomyopathy or hyperactive angiogenesis observed in mice with broad spectrum conditional Hif-p4h-2 inactivation. We focused here on the effects of chronic Hif-p4h-2 deficiency in the heart. Hif-1 and Hif-2 were stabilized, and the mRNA levels of glucose transporter-1, several enzymes of glycolysis, pyruvate dehydrogenase kinase 1, angiopoietin-2, and adrenomedullin were increased in the Hif-p4h-2(gt/gt) hearts. When isolated Hif-p4h-2(gt/gt) hearts were subjected to ischemia-reperfusion, the recovery of mechanical function and coronary flow rate was significantly better than in wild type, while cumulative release of lactate dehydrogenase reflecting the infarct size was reduced. The preischemic amount of lactate was increased, and the ischemic versus preischemic [CrP]/[Cr] and [ATP] remained at higher levels in Hif-p4h-2(gt/gt) hearts, indicating enhanced glycolysis and an improved cellular energy state. Our data suggest that chronic stabilization of Hif-1alpha and Hif-2alpha by genetic knockdown of Hif-p4h-2 promotes cardioprotection by induction of many genes involved in glucose metabolism, cardiac function, and blood pressure.

    The Journal of biological chemistry 2010;285;18;13646-57

  • Triosephosphate isomerase activity-deficient mice show haemolytic anaemia in homozygous condition.

    Pretsch W

    Institute of Human Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, D-85764 Neuherberg, Germany. pretsch@helmholtz-muenchen.de

    A triosephosphate isomerase (TPI) mutant, Tpi1(a-m6Neu), with approximately 57% residual enzyme activity in blood compared with wild-type was detected among offspring of triethylenemelamine-treated male mice. Homozygous mutants with about 13% residual enzyme activity were recovered in progeny of inter se matings of heterozygotes. The loss of TPI activity was evident both in blood and in other tissue extracts. Values for haematocrit, haemoglobin, number of red blood cells (RBC), mean corpuscular volume of RBC, mean corpuscular haemoglobin concentration and spleen weight show significant differences between wild-type animals and homozygous mutants. Sequence analysis revealed a substitution (c.A149G) in the Tpi1 gene. This mutation results in an Asp to Gly substitution at codon 49 in exon 2 at a highly conserved position located in the functional domain of the TPI protein which is responsible for the correct dimerization of the subunits. As a potential animal model, Tpi1(a-m6Neu) represents the only available TPI-deficient homozygous viable mouse mutation.

    Genetics research 2009;91;1;1-4

  • An analysis of expression patterns of genes encoding proteins with catalytic activities.

    Cankaya M, Hernandez AM, Ciftci M, Beydemir S, Ozdemir H, Budak H, Gulcin I, Comakli V, Emircupani T, Ekinci D, Kuzu M, Jiang Q, Eichele G and Kufrevioglu OI

    Genes and Behavior Department, Max Planck Institute of Biophysical Chemistry, Goettingen, Germany. mcankay@gwdg.de <mcankay@gwdg.de&gt;

    Background: In situ hybridization (ISH) is a powerful method for visualizing gene expression patterns at the organismal level with cellular resolution. When automated, it is capable of determining the expression of a large number of genes.

    Results: The expression patterns of 662 genes that encode enzymes were determined by ISH in the mid-gestation mouse embryo, a stage that models the complexity of the adult organism. Forty-five percent of transcripts encoding metabolic enzymes (n = 297) showed a regional expression pattern. A similar percentage was found for the 190 kinases that were also analyzed. Many mRNAs encoding glycolytic and TCA cycle enzymes exhibited a characteristic expression pattern. The annotated expression patterns were deposited on the Genepaint database and are retrievable by user-defined queries including gene name and sites of expression.

    Conclusion: The 662 expression patterns discussed here comprised gene products with activities associated with catalysis. Preliminary analysis of these data revealed that a significant number of genes encoding housekeeping functions such as biosynthesis and catabolism were expressed regionally, so they could be used as tissue-specific gene markers. We found no difference in tissue specificity between mRNAs encoding housekeeping functions and those encoding components of signal transduction pathways, as exemplified by the kinases.

    BMC genomics 2007;8;232

  • Endogenously nitrated proteins in mouse brain: links to neurodegenerative disease.

    Sacksteder CA, Qian WJ, Knyushko TV, Wang H, Chin MH, Lacan G, Melega WP, Camp DG, Smith RD, Smith DJ, Squier TC and Bigelow DJ

    Cell Biology and Biochemistry Group, Pacific Northwest National Laboratory, Richland, Washington 99352, USA.

    Increased abundance of nitrotyrosine modifications of proteins have been documented in multiple pathologies in a variety of tissue types and play a role in the redox regulation of normal metabolism. To identify proteins sensitive to nitrating conditions in vivo, a comprehensive proteomic data set identifying 7792 proteins from a whole mouse brain, generated by LC/LC-MS/MS analyses, was used to identify nitrated proteins. This analysis resulted in the identification of 31 unique nitrotyrosine sites within 29 different proteins. More than half of the nitrated proteins that have been identified are involved in Parkinson's disease, Alzheimer's disease, or other neurodegenerative disorders. Similarly, nitrotyrosine immunoblots of whole brain homogenates show that treatment of mice with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), an experimental model of Parkinson's disease, induces an increased level of nitration of the same protein bands observed to be nitrated in brains of untreated animals. Comparing sequences and available high-resolution structures around nitrated tyrosines with those of unmodified sites indicates a preference of nitration in vivo for surface accessible tyrosines in loops, a characteristic consistent with peroxynitrite-induced tyrosine modification. In addition, most sequences contain cysteines or methionines proximal to nitrotyrosines, contrary to suggestions that these amino acid side chains prevent tyrosine nitration. More striking is the presence of a positively charged moiety near the sites of nitration, which is not observed for non-nitrated tyrosines. Together, these observations suggest a predictive tool of functionally important sites of nitration and that cellular nitrating conditions play a role in neurodegenerative changes in the brain.

    Funded by: NCRR NIH HHS: RR018522; NIA NIH HHS: AG12993, AG18013; NIDA NIH HHS: DA015802; NINDS NIH HHS: NS050148

    Biochemistry 2006;45;26;8009-22

  • Gene expression in pharyngeal arch 1 during human embryonic development.

    Cai J, Ash D, Kotch LE, Jabs EW, Attie-Bitach T, Auge J, Mattei G, Etchevers H, Vekemans M, Korshunova Y, Tidwell R, Messina DN, Winston JB and Lovett M

    Institute of Genetic Medicine, Johns Hopkins University, 733 N. Broadway, Baltimore, MD 21205, USA.

    Craniofacial abnormalities are one of the most common birth defects in humans, but little is known about the human genes that control these important developmental processes. To identify relevant genes, we analyzed transcription profiles of human pharyngeal arch 1 (PA1), a conserved embryonic structure that develops into the palate and jaw. Using microdissected, normal human craniofacial structures, we constructed 12 SAGE (serial analysis of gene expression) libraries and sequenced 606 532 tags. We also performed Affymetrix microarray analysis on 25 craniofacial targets. Our data revealed not only genes "enriched" or differentially expressed in PA1 during fourth and fifth week of human development, but also 6927 genes newly identified to be expressed in human PA1. Many of these genes are involved in biosynthetic processes and have binding function and catalytic activity. We compared expression profiles of human genes with those of mouse homologs to look for genes more specific to human craniofacial development and found 766 genes expressed in human PA1, but not in mouse PA1. We also identified 1408 genes that were expressed in mouse as well as human PA1 and could be useful in creating mouse models for human conditions. We confirmed conservation of some human PA1 expression patterns in mouse embryonic samples with whole mount in situ hybridization and real-time RT-PCR. This comprehensive approach to expression profiling gives insights into the early development of the craniofacial region and provides markers for developmental structures and candidate genes, including SET and CCT3, for diseases such as orofacial clefting and micrognathia.

    Funded by: NIDCR NIH HHS: N01 DE 92630; NIGMS NIH HHS: T32 GM 07814

    Human molecular genetics 2005;14;7;903-12

  • Libraries enriched for alternatively spliced exons reveal splicing patterns in melanocytes and melanomas.

    Watahiki A, Waki K, Hayatsu N, Shiraki T, Kondo S, Nakamura M, Sasaki D, Arakawa T, Kawai J, Harbers M, Hayashizaki Y and Carninci P

    Genome Science Laboratory, RIKEN, Wako main campus, 2-1 Hirosawa, Wako, Saitama, 351-0198 Japan.

    It is becoming increasingly clear that alternative splicing enables the complex development and homeostasis of higher organisms. To gain a better understanding of how splicing contributes to regulatory pathways, we have developed an alternative splicing library approach for the identification of alternatively spliced exons and their flanking regions by alternative splicing sequence enriched tags sequencing. Here, we have applied our approach to mouse melan-c melanocyte and B16-F10Y melanoma cell lines, in which 5,401 genes were found to be alternatively spliced. These genes include those encoding important regulatory factors such as cyclin D2, Ilk, MAPK12, MAPK14, RAB4, melastatin 1 and previously unidentified splicing events for 436 genes. Real-time PCR further identified cell line-specific exons for Tmc6, Abi1, Sorbs1, Ndel1 and Snx16. Thus, the ASL approach proved effective in identifying splicing events, which suggest that alternative splicing is important in melanoma development.

    Nature methods 2004;1;3;233-9

  • The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

    Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Morrin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J and MGC Project Team

    The National Institutes of Health's Mammalian Gene Collection (MGC) project was designed to generate and sequence a publicly accessible cDNA resource containing a complete open reading frame (ORF) for every human and mouse gene. The project initially used a random strategy to select clones from a large number of cDNA libraries from diverse tissues. Candidate clones were chosen based on 5'-EST sequences, and then fully sequenced to high accuracy and analyzed by algorithms developed for this project. Currently, more than 11,000 human and 10,000 mouse genes are represented in MGC by at least one clone with a full ORF. The random selection approach is now reaching a saturation point, and a transition to protocols targeted at the missing transcripts is now required to complete the mouse and human collections. Comparison of the sequence of the MGC clones to reference genome sequences reveals that most cDNA clones are of very high sequence quality, although it is likely that some cDNAs may carry missense variants as a consequence of experimental artifact, such as PCR, cloning, or reverse transcriptase errors. Recently, a rat cDNA component was added to the project, and ongoing frog (Xenopus) and zebrafish (Danio) cDNA projects were expanded to take advantage of the high-throughput MGC pipeline.

    Funded by: PHS HHS: N01-C0-12400

    Genome research 2004;14;10B;2121-7

  • Chromosomal localization, hematologic characterization, and iron metabolism of the hereditary erythroblastic anemia (hea) mutant mouse.

    White RA, McNulty SG, Roman S, Garg U, Wirtz E, Kohlbrecher D, Nsumu NN, Pinson D, Gaedigk R, Blackmore K, Copple A, Rasul S, Watanabe M and Shimizu K

    Children's Mercy Hospitals and Clinics, Pediatric Research Center, 4th floor, 2401 Gillham Rd, Kansas City, MO 64108, USA. rwhite@cmh.edu

    Understanding iron metabolism has been enhanced by identification of genes for iron deficiency mouse mutants. We characterized the genetics and iron metabolism of the severe anemia mutant hea (hereditary erythroblastic anemia), which is lethal at 5 to 7 days. The hea mutation results in reduced red blood cell number, hematocrit, and hemoglobin. The hea mice also have elevated Zn protoporphyrin and serum iron. Blood smears from hea mice are abnormal with elevated numbers of smudge cells. Aspects of the hea anemia can be transferred by hematopoietic stem cell transplantation. Neonatal hea mice show a similar hematologic phenotype to the flaky skin (fsn) mutant. We mapped the hea gene near the fsn locus on mouse chromosome 17 and show that the mutants are allelic. Both tissue iron overloading and elevated serum iron are also found in hea and fsn neonates. There is a shift from iron overloading to iron deficiency as fsn mice age. The fsn anemia is cured by an iron-supplemented diet, suggesting an iron utilization defect. When this diet is removed there is reversion to anemia with concomitant loss of overloaded iron stores. We speculate that the hea/fsn gene is required for iron uptake into erythropoietic cells and for kidney iron reabsorption.

    Blood 2004;104;5;1511-8

  • GenePaint.org: an atlas of gene expression patterns in the mouse embryo.

    Visel A, Thaller C and Eichele G

    Max Planck Institute of Experimental Endocrinology, Feodor-Lynen-Strasse 7, D-30625 Hannover, Germany.

    High-throughput instruments were recently developed to determine gene expression patterns on tissue sections by RNA in situ hybridization. The resulting images of gene expression patterns, chiefly of E14.5 mouse embryos, are accessible to the public at http://www.genepaint.org. This relational database is searchable for gene identifiers and RNA probe sequences. Moreover, patterns and intensity of expression in approximately 100 different embryonic tissues are annotated and can be searched using a standardized catalog of anatomical structures. A virtual microscope tool, the Zoom Image Server, was implemented in GenePaint.org and permits interactive zooming and panning across approximately 15,000 high-resolution images.

    Nucleic acids research 2004;32;Database issue;D552-6

  • Wnk1 kinase deficiency lowers blood pressure in mice: a gene-trap screen to identify potential targets for therapeutic intervention.

    Zambrowicz BP, Abuin A, Ramirez-Solis R, Richter LJ, Piggott J, BeltrandelRio H, Buxton EC, Edwards J, Finch RA, Friddle CJ, Gupta A, Hansen G, Hu Y, Huang W, Jaing C, Key BW, Kipp P, Kohlhauff B, Ma ZQ, Markesich D, Payne R, Potter DG, Qian N, Shaw J, Schrick J, Shi ZZ, Sparks MJ, Van Sligtenhorst I, Vogel P, Walke W, Xu N, Zhu Q, Person C and Sands AT

    Lexicon Genetics, 8800 Technology Forest Place, The Woodlands, TX 77381, USA. brian@lexgen.com

    The availability of both the mouse and human genome sequences allows for the systematic discovery of human gene function through the use of the mouse as a model system. To accelerate the genetic determination of gene function, we have developed a sequence-tagged gene-trap library of >270,000 mouse embryonic stem cell clones representing mutations in approximately 60% of mammalian genes. Through the generation and phenotypic analysis of knockout mice from this resource, we are undertaking a functional screen to identify genes regulating physiological parameters such as blood pressure. As part of this screen, mice deficient for the Wnk1 kinase gene were generated and analyzed. Genetic studies in humans have shown that large intronic deletions in WNK1 lead to its overexpression and are responsible for pseudohypoaldosteronism type II, an autosomal dominant disorder characterized by hypertension, increased renal salt reabsorption, and impaired K+ and H+ excretion. Consistent with the human genetic studies, Wnk1 heterozygous mice displayed a significant decrease in blood pressure. Mice homozygous for the Wnk1 mutation died during embryonic development before day 13 of gestation. These results demonstrate that Wnk1 is a regulator of blood pressure critical for development and illustrate the utility of a functional screen driven by a sequence-based mutagenesis approach.

    Proceedings of the National Academy of Sciences of the United States of America 2003;100;24;14109-14

  • Gris1, a new common integration site in Graffi murine leukemia virus-induced leukemias: overexpression of a truncated cyclin D2 due to alternative splicing.

    Denicourt C, Kozak CA and Rassart E

    Laboratoire de Biologie Moléculaire, Département des Sciences Biologiques, Université du Québec à Montréal, Canada.

    The Graffi murine leukemia virus is a nondefective ecotropic retrovirus that was originally reported to induce myeloid leukemia in some strains of mice (A. Graffi, Ann. N.Y. Acad. Sci. 68:540-558, 1957). Using provirus-flanking sequences as DNA probes, we identified a new common retroviral integration site called Gris1 (for Graffi integration site 1). Viral integrations in Gris1 were detected in 13% of the tumors analyzed. The Gris1 locus was mapped to the distal region of mouse chromosome 6, 85 kb upstream of the cyclin D2 gene. Such viral integration in Gris1 causes overexpression of the normal 6.5-kb major transcript of cyclin D2 but also induces the expression of a new, alternatively spliced 1.1-kb transcript from the cyclin D2 gene that encodes a truncated cyclin D2 of 17 kDa. The expression of this 1.1-kb transcript is specific to tumors in which Gris1 is rearranged but is also detected at low levels in normal tissue.

    Journal of virology 2003;77;1;37-44

  • Genome-wide expression profiling of mid-gestation placenta and embryo using a 15,000 mouse developmental cDNA microarray.

    Tanaka TS, Jaradat SA, Lim MK, Kargul GJ, Wang X, Grahovac MJ, Pantano S, Sano Y, Piao Y, Nagaraja R, Doi H, Wood WH, Becker KG and Ko MS

    Laboratory of Genetics and DNA Array Unit, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224-6820, USA.

    cDNA microarray technology has been increasingly used to monitor global gene expression patterns in various tissues and cell types. However, applications to mammalian development have been hampered by the lack of appropriate cDNA collections, particularly for early developmental stages. To overcome this problem, a PCR-based cDNA library construction method was used to derive 52,374 expressed sequence tags from pre- and peri-implantation embryos, embryonic day (E) 12.5 female gonad/mesonephros, and newborn ovary. From these cDNA collections, a microarray representing 15,264 unique genes (78% novel and 22% known) was assembled. In initial applications, the divergence of placental and embryonic gene expression profiles was assessed. At stage E12.5 of development, based on triplicate experiments, 720 genes (6.5%) displayed statistically significant differences in expression between placenta and embryo. Among 289 more highly expressed in placenta, 61 placenta-specific genes encoded, for example, a novel prolactin-like protein. The number of genes highly expressed (and frequently specific) for placenta has thereby been increased 5-fold over the total previously reported, illustrating the potential of the microarrays for tissue-specific gene discovery and analysis of mammalian developmental programs.

    Proceedings of the National Academy of Sciences of the United States of America 2000;97;16;9127-32

  • Enzyme-activity mutants in Mus musculus. I. Phenotypic description and genetic characterization of ethylnitrosourea-induced mutations.

    Pretsch W

    GSF-National Research Center for Environment and Health, Institute of Mammalian Genetics, Ingolstädter Landstrasse 1, D-85764 Neuherberg, Germany. pretsch@gsf.de

    The specific activity of erythrocyte enzymes was measured to detect gene mutations in F(1)-offspring of male mice treatment with different doses (80, 160, or 250 mg/kg body weight) of ethylnitrosourea (ENU). Altogether 13,230 offspring were screened for 10 enzyme activities. Mutants with reduced activity as well as mutants with enhanced activity were found. Of the 36 independently observed mutations, 20 were homozygous lethal. Genetic and biochemical characterizations were routinely performed. These mutants provide insight into the mechanism of ENU mutagenesis and can serve as models for structure-function studies of the corresponding enzymes.

    Mammalian genome : official journal of the International Mammalian Genome Society 2000;11;7;537-42

  • Genetic mapping and analysis of mouse p27Kip1 gene as Pas1 candidate gene.

    Gariboldi M, De Gregorio L, Manenti G and Dragani TA

    Department of Experimental Oncology, Istituto Nazionale Tumori, Milan, Italy.

    Mammalian genome : official journal of the International Mammalian Genome Society 2000;11;4;338-9

  • Characterization of a novel receptor that maps near the natural killer gene complex: demonstration of carbohydrate binding and expression in hematopoietic cells.

    Fernandes MJ, Finnegan AA, Siracusa LD, Brenner C, Iscove NN and Calabretta B

    Thomas Jefferson University, Department of Microbiology and Immunology, Kimmel Cancer Institute, Philadelphia, Pennsylvania 19107, USA.

    A novel type II integral membrane protein has been identified in the course of screening for genes overexpressed in a mouse model of chronic myelogenous leukemia blast crisis. This new protein, designated NKCL, consists of a 210-amino acid polypeptide with a short, NH2-terminal cytoplasmic tail of 17 amino acids preceding a transmembrane domain and a COOH-terminal extracellular region. The COOH-terminal 132 amino acids bear typical features of the C-type animal lectin carbohydrate-recognition domain. The Nkcl gene is unique in that it maps just proximal to the region of the genome that encodes group V members of the C-type animal lectin family near the natural killer gene complex on mouse chromosome 6, but its protein product also has features of several group II C-type animal lectins. Most notably, it has a complete Ca2+-binding site 2, which forms part of the sugar-binding site in other members of the family, and binds mannose in a Ca2+-dependent manner. Moreover, its expression is not restricted to natural killer cells, as reported for the majority of group V lectins. Nkcl is expressed in pluripotent myeloid precursors, precursor and mature macrophages, and neutrophils.

    Funded by: NCI NIH HHS: CA21124, CA46782

    Cancer research 1999;59;11;2709-17

  • Comparative sequence analysis of a gene-rich cluster at human chromosome 12p13 and its syntenic region in mouse chromosome 6.

    Ansari-Lari MA, Oeltjen JC, Schwartz S, Zhang Z, Muzny DM, Lu J, Gorrell JH, Chinault AC, Belmont JW, Miller W and Gibbs RA

    Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.

    The Human Genome Project has created a formidable challenge: the extraction of biological information from extensive amounts of raw sequence. With the increasing availability of genomic sequence from other species, one approach to extracting coding and regulatory element information is through cross-species sequence comparison. To assess the strengths and weaknesses of this methodology for large-scale sequence analysis, 227 kb of mouse sequence syntenic to a gene-rich cluster on human chromosome 12p13 was obtained. Primarily through percent identity plots (PIPs) of SIM comparative sequence alignments, the sequence of coding regions, putative alternative exons, conserved noncoding regions, and correlation in repetitive element insertions were easily determined. The analysis demonstrated that the number, order, and orientation of all 17 genes are conserved between the two species, whereas two human pseudogenes are absent in mouse. In addition, apart from MIRs, no direct correlation of distribution or position of the majority of repetitive elements between the two species is seen. Finally, in examining the synonymous and nonsynonymous substitution rates in the conserved genes, a large variation in nonsynonymous rates is observed indicating that the genes in this region are diverging at different rates. This study indicates the utility and strength of large-scale cross-species sequence comparisons in the extraction of biological information from raw sequence, especially when combined with other computational tools such as GRAIL and BLAST.

    Funded by: NHGRI NIH HHS: R01 HG01459; NLM NIH HHS: LM05110

    Genome research 1998;8;1;29-40

  • The gene encoding sepiapterin reductase is located in central mouse chromosome 6.

    Kim J, Park YS, Chung JH and Stubbs L

    Life Sciences Division, Oak Ridge National Laboratory, Tennessee 37831-8077, USA.

    Mammalian genome : official journal of the International Mammalian Genome Society 1997;8;12;942

  • High-resolution linkage map in the proximity of the host resistance locus Cmv1.

    Depatie C, Muise E, Lepage P, Gros P and Vidal SM

    Center for the Study of Host Resistance, McGill University, Montreal General Hospital, Quebec, Canada.

    The mouse chromosome 6 locus Cmv1 controls replication of mouse Cytomegalovirus (MCMV) in the spleen of the infected host. In our effort to clone Cmv1, we have constructed a high-resolution genetic linkage map in the proximity of the gene. For this, a total of 45 DNA markers corresponding to either cloned genes or microsatellites were mapped within a 7.9-cM interval overlapping the Cmv1 region. We have followed the cosegregation of these markers with respect to Cmv1 in a total of 2248 backcross mice from a preexisting interspecific backcross panel of 281 (Mus spretus x C57BL/6J)F1 x C57BL/6J and 2 novel panels of 989 (A/ J x C57BL6)F1 x A/J and 978 (BALB/c x C57BL/6J)F1 x BALB/c segregating Cmv1. Combined pedigree analysis allowed us to determine the following gene order and intergene distances (in cM) on the distal region of mouse chromosome 6: D6Mit216-(1.9)-D6Mit336-(2.2)- D6Mit218-(1.0)-D6Mit52-(0.5)-D6Mit194-(0.2)-Nkrp 1/ D6Mit61/135/257/289/338-(0.4)-Cmv1/Ly49A/D6Mit370++ +- (0.3)-Prp/Kap/D6Mit13/111/219-(0.3)-Tel/D6Mit374/290/ 220/196/195/110-(1.1)-D6Mit25. Therefore, the minimal genetic interval for Cmv1 of 0.7 cM is defined by 13 tightly linked markers including 2 markers, Ly49A and D6Mit370, that did not show recombination with Cmv1 in 1967 meioses analyzed; the proximal limit of the Cmv1 domain was defined by 8 crossovers between Nkrp1/ D6Mit61/135/257/289/338 and Cmv1/Ly49A/D6Mit370, and the distal limit was defined by 5 crossovers between Cmv1/Ly49A/D6Mit370 and Prp/Kap/D6Mit13/111/219. This work demonstrates tight linkage between Cmv1 and genes from the natural killer complex (NKC), such as Nkrp1 and Ly49A, suggesting that Cmv1 may represent an NK cell recognition structure encoded in the NKC region.

    Genomics 1997;39;2;154-63

  • Megencephaly: a new mouse mutation on chromosome 6 that causes hypertrophy of the brain.

    Donahue LR, Cook SA, Johnson KR, Bronson RT and Davisson MT

    Jackson Laboratory, Bar Harbor, Maine 04609, USA.

    Megencephaly, enlarged brain, occurs in several acquired and inherited human diseases including Sotos syndrome, Robinow syndrome, Canavan's disease, and Alexander disease. This defect can be distinguished from macrocephaly, an enlarged head, which usually occurs as a consequence of congenital hydrocephalus. The pathology of megencephaly in humans has not been well defined, nor has the defect been reported to occur spontaneously in any other species. In this report we describe a recessive mutation in the mouse that results in a 25% increase in brain size in the first 8 months of life. We have determined that the megencephaly is characterized by overall hypertrophy of the brain, and not by hyperplasia of particular cell types or by hypertrophy of a singular tissue compartment. Edema and hydrocephalus are absent. This mutation has been mapped to mid-distal mouse Chromosome (Chr) 6 in a region homologous with human Chr 12.

    Funded by: NCRR NIH HHS: RR01183; NIGMS NIH HHS: GM46697; NINDS NIH HHS: NS30153; ...

    Mammalian genome : official journal of the International Mammalian Genome Society 1996;7;12;871-6

  • Localization of the guanylyl cyclase C gene to mouse chromosome 6 and human chromosome 12p12.

    Mann EA, Swenson ES, Copeland NG, Gilbert DJ, Jenkins NA, Taguchi T, Testa JR and Giannella RA

    Division of Digestive Diseases, Veterans Affairs Medical Center, Cincinnati, Ohio, 45220, USA.

    Funded by: NCI NIH HHS: CA-06927

    Genomics 1996;34;2;265-7

  • The murine lymphotoxin-beta receptor cDNA: isolation by the signal sequence trap and chromosomal mapping.

    Nakamura T, Tashiro K, Nazarea M, Nakano T, Sasayama S and Honjo T

    Department of Medical Chemistry, Faculty of Medicine, Kyoto University, Japan.

    To isolate novel molecules involved in intercellular signaling during mouse embryogenesis, we employed the signal sequence trap (SST) method, a newly developed strategy for cloning secreted proteins and type I membrane proteins. We constructed an SST cDNA library of mouse embryonic heart mRNA, screened 2000 clones, and acquired 1 positive clone that appeared to contain the signal sequence. Homology searches revealed that this clone encodes the mouse lymphotoxin-beta receptor (LT beta-R). The deduced amino acid sequence of the mouse LT beta-R was 66% identical to that of the human LT beta-R. Northern analysis of various organs in adult mice showed that expression levels of LT beta-R mRNA were strong in lung, liver, and kidney, moderate in heart and testis, but weak in brain, thymus, spleen, and lymph nodes. Since the mouse LT beta-R was already expressed in 7-day-postcoitus embryo, the LT beta/LT beta-R system might have some functions in early embryogenesis. We performed chromosomal mapping of the murine LT beta-R gene by linkage analysis with recombinant inbred mouse strains and found that its locus is very close to the tumor necrosis factor receptor 1 gene on chromosome 6.

    Genomics 1995;30;2;312-9

  • Epithelial sodium channel genes Scnn1b and Scnn1g are closely linked on distal mouse chromosome 7.

    Brooker DR, Kozak CA and Kleyman TR

    Department of Medicine, University of Pennsylvania, Philadelphia 19104-6144, USA.

    The chromosomal localizations of Scnn1b and Scnn1g, genes corresponding to the beta- and gamma-subunits, respectively, of an epithelial non-voltage-gated amiloride-sensitive sodium channel, were determined by analyses of two sets of multilocus crosses using probes generated by polymerase chain reaction and a mouse kidney cortical collecting tubule cell line (M1). Scnn1b and Scnn1g were determined to be closely linked on distal mouse chromosome 7, showing no recombination with Zp2, whereas the gene for the alpha-subunit, Scnn1a, was confirmed to map to distal mouse chromosome 6.

    Funded by: NIDDK NIH HHS: DK07006

    Genomics 1995;29;3;784-6

  • Localization of alpha 4m integrin at sites of mesenchyme condensation during embryonic mouse development.

    Jaspers M, Wu RR, Van der Schueren B and Cassiman JJ

    Center for Human Genetics, University of Leuven, Belgium.

    The expression and distribution of the murine alpha 4 (alpha 4m) integrin subunit and of one of its ligands, VCAM-1, were examined in the developing mouse embryo at different development stages. Transcription of the mRNA was investigated by in situ hybridization using single-stranded sense and anti-sense cDNA probes and by Northern blotting. In parallel sections integrin was identified by immunohistochemistry using the alpha 4m-specific antibody R1/2. In general both methods gave similar distributions. The results demonstrate that alpha 4m and vascular cell adhesion molecule-1 (VCAM-1) are expressed in mouse embryonic liver (E11-E15) and are developmentally down-regulated, consistent with the haematopoietic properties of embryonic liver. Developmental-stage-dependent expression of alpha 4m was also observed in lymphoid organs, such as spleen and thymus, and in some non-lymphoid organs or tissues, such as skeletal and tongue muscles, smooth muscles of the blood vessels, the outflow tract of the embryonic heart, the papilla of the tooth, the glomeruli of the kidney and the stroma of the gonads. In the latter tissues, the expression of alpha 4m correlated with the transient condensation of particular mesenchymal structures. We also confirm that VCAM-1 and alpha 4 beta 1 are co-distributed only in some tissues, suggesting that during mouse development, VLA-4 interacts mainly with another ligand, probably fibronectin.

    Differentiation; research in biological diversity 1995;59;2;79-86

  • Mapping of the Hmg1 gene and of seven related sequences in the mouse.

    Gariboldi M, De Gregorio L, Ferrari S, Manenti G, Pierotti MA, Bianchi ME and Dragani TA

    Division of Experimental Oncology A, Istituto Nazionale Tumori, Milano, Italy.

    The High Mobility Group 1 protein (HMG1) is an abundant and highly conserved chromosomal protein. Mouse HMG1 is encoded by the Hmg1 gene, containing four introns, but the murine genome contains many related sequences that are mostly retrotransposed pseudogenes. By using an interspecific cross, we have mapped the functional Hmg1 gene on mouse Chromosome (Chr) 5 and seven Hmg1-related sequences on Chrs 6, 8, 17, 18, and X.

    Funded by: Telethon: A.007

    Mammalian genome : official journal of the International Mammalian Genome Society 1995;6;9;581-5

  • Molecular analysis of four ENU induced triosephosphate isomerase null mutants in Mus musculus.

    Zingg BC, Pretsch W and Mohrenweiser HW

    Biology and Biotechnology Research Program, Lawrence Livermore National Laboratory, Livermore, CA 94550, USA.

    Four ENU-induced mutations were previously identified at the triosephosphate isomerase (TPI) locus in mouse germinal mutation experiments. Each of the mutants is associated with a 50% loss of enzymatic activity in the F1 (heterozygous) animals. Exons of the TPI gene from control mice and heterozygous mutant mice were PCR amplified and sequenced as necessary to determine the molecular lesion in the mutant alleles. Mutants Tpi*M-1NEU and Tpi*M-2NEU carried the same T:A to A:T transversion in exon 6, resulting in a Leu to Gln substitution at residue 192. Amino acid residue 192 is located in alpha-helix H6 of the protein. Tpi*M-4NEU contained a T:A to A:T transversion within the codon for residue 162 in exon 5, also causing a Leu to Gln substitution. This mutation is located at the beginning of beta-strand B6, within a highly conserved sequence region surrounding the active site residue Glu 165. Sequence analysis of Tpi*M-3NEU revealed an A:T to C:G transversion, changing the stop codon to a codon for Cys, with the resulting addition of 19 predominantly hydrophobic amino acids to the protein. All four mutations occurred at an A:T base pair. In each case, the mutation site was flanked on both sides by G:C base pairs. Each of the sequence alterations has a potential impact on the structure of the TPI protein that is consistent with the existence of a null allele. In addition to providing insight into the molecular basis of ENU induced germ cell mutations and the differences in mutation spectra among organisms, these mutants represent models for structure-function studies of this highly conserved enzyme.

    Mutation research 1995;328;2;163-73

  • Identification and genetic mapping of 151 dispersed members of 16 ribosomal protein multigene families in the mouse.

    Johnson KR, Cook SA and Davisson MT

    Jackson Laboratory, Bar Harbor, Maine 04609.

    More than 150 individual members of 16 ribosomal protein multigene families were identified as DNA restriction fragments and genetically mapped. The ribosomal protein gene-related sequences are widely dispersed throughout the mouse genome. Map positions were determined by analysis of 144 progeny mice from both an interspecific (C57BL/6J x SPRET/Ei)F1 x SPRET/Ei and an intersubspecific (C57BL/6J x CAST/Ei)F1 x C57BL/6J backcross. In addition, 30 members of the multigene families encoding PGK1 ODC, and TPI, including five new loci for ODC and one new locus for TPI, were characterized and mapped. Interspecific backcross linkage data for 29 nonecotropic murine leukemia retroviruses endogenous to C57BL/6J mice are also reported. Transmission ratio distortions and recombination frequencies are compared between the two backcrosses.

    Funded by: NCI NIH HHS: CA34196; NCRR NIH HHS: RR01183; NIGMS NIH HHS: GM46697

    Mammalian genome : official journal of the International Mammalian Genome Society 1994;5;11;670-87

  • Comparative mapping of the actin-binding protein 280 genes in human and mouse.

    Gariboldi M, Maestrini E, Canzian F, Manenti G, De Gregorio L, Rivella S, Chatterjee A, Herman GE, Archidiacono N, Antonacci R et al.

    Division of Experimental Oncology A, Istituto Nazionale Tumori, Milan, Italy.

    Two genes encode actin-binding protein 280 isoforms. ABP-280 or filamin (FLN1) is present in the cytoskeleton of many cell types, whereas expression of FLN2 is limited to skeletal muscle and heart. FLN1 maps to human chromosome Xq28, and, by physical mapping in YAC clones, we have mapped the homologous murine locus (Fln1) to mouse chromosome X, in a region of syntenic homology with human chromosome X. We mapped FLN2 to human chromosome 7q32-q35 by analysis of somatic cell hybrids containing portions of chromosome 7, and, by using a mapping panel from an interspecific murine cross, we mapped the corresponding murine locus (Fln2) to murine chromosome 6 in a region homologous to human chromosome 7.

    Funded by: Telethon: 271

    Genomics 1994;21;2;428-30

  • Chromosomal mapping in the mouse of eight K(+)-channel genes representing the four Shaker-like subfamilies Shaker, Shab, Shaw, and Shal.

    Klocke R, Roberds SL, Tamkun MM, Gronemeier M, Augustin A, Albrecht B, Pongs O and Jockusch H

    Developmental Biology Unit, University of Bielefeld, Federal Republic of Germany.

    The four Shaker-like subfamilies of Shaker-, Shab-, Shaw-, and Shal-related K+ channels in mammals have been defined on the basis of their sequence homologies to the corresponding Drosophila genes. Using interspecific backcrosses between Mus musculus and Mus spretus, we have chromosomally mapped in the mouse the Shaker-related K(+)-channel genes Kcna1, Kcna2, Kcna4, Kcna5, and Kcna6; the Shab-related gene Kcnb1; the Shaw-related gene Kcnc4; and the Shal-related gene Kcnd2. The following localizations were determined: Chr 2, cen-Acra-Kcna4-Pax-6-a-Pck-1-Kras-3-Kcn b1 (corresponding human Chrs 11p and 20q, respectively); Chr 3, cen-Hao-2-(Kcna2, Kcnc4)-Amy-1 (human Chr 1); and Chr 6, cen-Cola-2-Met-Kcnd2-Cpa-Tcrb-adr/Clc-1-Hox-1.1-Myk - 103-Raf-1-(Tpi-1, Kcna1, Kcna5, Kcna6) (human Chrs 7q and 12p, respectively). Thus, there is a cluster of at least three Shaker-related K(+)-channel genes on distal mouse Chr 6 and a cluster on Chr 2 that at least consists of one Shaker-related and one Shaw-related gene. The three other K(+)-channel genes are not linked to each other. The map positions of the different types of K(+)-channel genes in the mouse are discussed in relation to those of their homologs in man and to hereditary diseases of mouse and man that might involve K+ channels.

    Genomics 1993;18;3;568-74

  • The gene map of the Norway rat (Rattus norvegicus) and comparative mapping with mouse and man.

    Levan G, Szpirer J, Szpirer C, Klinga K, Hanson C and Islam MQ

    Department of Genetics, University of Gothenburg, Sweden.

    The current status of the rat gene map is presented. Mapping information is now available for a total of 214 loci and the number of mapped genes is increasing steadily. The corresponding number of loci quoted at HGM10 was 128. Genes have been assigned to 20 of the 22 chromosomes in the rat. Some aspects of comparative mapping with mouse and man are also discussed. It was found that there is a good correlation between the morphological homologies detectable in rat and mouse chromosomes, on the one hand, and homology at the gene level on the other. For 10 rat synteny groups all the genes so far mapped are syntenic also in the mouse. For the remaining rat synteny groups it appears that the majority of the genes will be syntenic on specific (homologous) mouse chromosomes, with only a few genes dispersed to other members of the mouse karyotype. Furthermore, the data indicate that mouse chromosome 1 genetically corresponds to two rat chromosomes, viz., 9 and 13, equalizing the difference in chromosome number between the two species. Further mappings will show whether the genetic homology will prove to be as extensive as these preliminary results indicate. As might be expected from evolutionary considerations, rat synteny groups are much more dispersed in the human genome. It is clear, however, that many groups of genes have remained syntenic during the period since man and rat shared a common ancestor. One further point was noted. In two cases groups of genes were syntenic in the mouse but dispersed to two chromosomes in rat and man, whereas in a third case a group of genes was syntenic in the rat but dispersed to two chromosomes in mouse and man. This finding argues in favor of the notion that the original gene groups were on separate ancestral chromosomes, which have fused in one rodent species but remained separate in the other and in man.

    Genomics 1991;10;3;699-718

  • A mutation resulting in increased triosephosphate isomerase activity in Mus musculus.

    Merkle S, Reitmeir P and Pretsch W

    GSF-Institut für Säugetiergenetik, Neuherberg, Federal Republic of Germany.

    A mutation resulting in increased triosephosphate isomerase (TPI) activity in blood was recovered in offspring of procarbazine hydrochloride-treated male mice. Breeding experiments indicated a codominant mode of expression. Compared to the wild type, heterozygous and homozygous mutants have mean erythrocyte TPI activities of approximately 140 and 190%, respectively. Besides blood and erythrocytes the increased activity is expressed to a similar degree in spleen, and to a lesser degree in liver, lung, kidney, muscle and brain. Enhanced activity was absent in the heart. Heterozygous and homozygous mutants are viable, fully fertile and exhibit no significant differences in haematological or other physiological traits studied. Biochemical investigations of TPI in both mutant genotypes revealed neither physicochemical nor kinetic differences compared to the wild type. Moreover, immunoinactivation studies showed no difference in the amount of antiplasma required to inactivate a constant amount of TPI activity in all three genotypes, strongly suggesting that the differences in enzyme activity are attributable to differing amounts of enzyme protein expressed per cell. Mapping studies indicated that the mutation is closely linked to the Gapd locus and consequently is located either adjacent to or within the Tpi-1 structural locus. It is hypothesized that the mutation affected a regulatory element contiguous to the Tpi-1 structural locus which acts by increasing the amount of TPI expressed.

    Genetical research 1991;57;2;139-45

  • Tpi-1 and Gapd are linked very closely on mouse chromosome 6.

    Pretsch W, Neuhäuser-Klaus A and Merkle S

    GSF-Institut für Säugetiergenetik, Neuherberg, Federal Republic of Germany.

    Mutations in the structural genes for triosephosphate isomerase and glyceraldehyde-3-phosphate dehydrogenase activity in the mouse, selected after mutagen treatment, were used to estimate the map distance between the two loci. It is shown that Tpi-1 and Gapd are closely linked on chromosome 6, with a recombination frequency of 0.1 +/- 0.1%.

    Genetical research 1991;57;1;37-40

  • Identification and applications of repetitive probes for gene mapping in the mouse.

    Siracusa LD, Jenkins NA and Copeland NG

    NCI-Frederick Cancer Research and Development Center, Mammalian Genetics Laboratory, Maryland 21702.

    Interspecific mouse hybrids that are viable and fertile provide a wealth of genetic variation that is useful for gene mapping. We are using this genetic variation to develop multilocus linkage maps of the mouse genome. As an outgrowth of this work, we have identified three repetitive probes that collectively identify 28 loci dispersed on 16 of the 19 mouse autosomes and the X chromosome. These loci establish a skeleton linkage map that can be used to detect linkage over much of the mouse genome. The molecular probes are derived from the mouse mammary tumor virus envelope gene, the ornithine decarboxylase gene, and the triose phosphate isomerase gene. The ability to scan the mouse genome quickly and efficiently in an interspecific cross using these three repetitive probes makes this system a powerful tool for identifying the chromosomal location of mutations that have yet to be cloned, mapping multigenic traits, and identifying recessive protooncogene loci associated with murine neoplastic disease. Ultimately, interspecific hybrids in conjunction with repetitive and single-copy probes will provide a rapid means to access virtually any gene of interest in the mouse genome at the molecular level.

    Funded by: NCI NIH HHS: N01-CO-74101; NIGMS NIH HHS: GM12721-01

    Genetics 1991;127;1;169-79

  • Nucleotide sequence of murine triosephosphate isomerase cDNA.

    Cheng J, Mielnicki LM, Pruitt SC and Maquat LE

    Department of Human Genetics, Roswell Park Cancer Institute, Buffalo, NY 14263.

    Funded by: NICHD NIH HHS: HD25419; NIDDK NIH HHS: DK33938

    Nucleic acids research 1990;18;14;4261

  • Characterization of triosephosphate isomerase mutants with reduced enzyme activity in Mus musculus.

    Merkle S and Pretsch W

    GSF-Institut für Sügetiergenetik, Neuherberg, Federal Republic of Germany.

    Four heterozygous triosephosphate isomerase (TPI) mutants with approximately 50% reduced activity in blood compared to wild type were detected in offspring of 1-ethyl-1-nitrosourea treated male mice. Breeding experiments displayed an autosomal, dominant mode of inheritance for the mutations. All mutations were found to be homozygous lethal at an early postimplantation stage of embryonic development, probably due to a total lack of TPI activity and consequently to the inability to utilize glucose as a source of metabolic energy. Although activity alteration was also found in liver, lung, kidney, spleen, heart, brain and muscle the TPI deficiency in heterozygotes has no influence on the following physiological traits: hematological parameters, plasma glucose, glucose consumption of blood cells, body weight and organo-somatic indices of liver, spleen, heart, kidney and lung. Biochemical investigations of TPI in the four mutant lines indicated no difference of physicochemical properties compared to the wild type. Results from immunoinactivation assays indicate that the decrease of enzyme activity corresponds to a decrease in the level of an immunologically active moiety. It is suggested that the mutations have affected the Tpi-1 structural locus and resulted in alleles which produce no detectable enzyme activity and no immunologically cross-reacting material. The study furthermore suggests one functional TPI gene per haploid genome in the erythrocyte and seven other tested organs of the mouse.

    Genetics 1989;123;4;837-44

  • An allele at the triose phosphate isomerase, Tpi-1 locus on chromosome 6 recovered from feral mice.

    Bulfield G, Ball ST and Peters J

    Genetical research 1987;50;3;239-43

  • Hox-1.6: a mouse homeo-box-containing gene member of the Hox-1 complex.

    Baron A, Featherstone MS, Hill RE, Hall A, Galliot B and Duboule D

    Laboratoire de Génétique Moléculaire des Eucaryotes du CNRS, Unité 184 de Biologie Moléculaire et de Génie Génétique de l'INSERM, Faculté de Médecine, Strasbourg, France.

    Hox-1.6, a mouse homeo-box-containing gene member of the Hox-1 complex, is described. The Hox-1.6 homeo-box shows more divergence than the other members of the complex with the Drosophila Antennapedia-like homeo-box class. This previously undescribed gene was studied with respect to its transcription pattern and was found to be expressed during mouse fetal development in an intestine-specific manner in adults, and in tumours or cell types exhibiting early endodermal-like differentiation. The study of embryonic partial Hox-1.6 cDNA clones revealed structural features common to other Drosophila and vertebrate homeo-box-containing genes, but also indicated that Hox-1.6 transcripts might display splicing patterns more complex than those known for other vertebrate homeo-genes. One of these cDNA clones contains a rather short open reading frame which would encode a protein of approximately 14.5 kd. The use of this clone as a probe for S1 nuclease mapping confirmed that different Hox-1.6 transcripts were present both in embryonic total RNA and in embryonal carcinoma cell cytoplasmic RNA. These various transcripts are probably generated by an alternative splicing mechanism and may thus encode a set of related proteins.

    The EMBO journal 1987;6;10;2977-86

  • Linear dose-response relationship of erythrocyte enzyme-activity mutations in offspring of ethylnitrosourea-treated mice.

    Charles DJ and Pretsch W

    The specific activity of 10 erythrocyte enzymes was measured to detect gene mutations in F1 offspring of male mice treated with 3 different doses of ethylnitrosourea (ENU). After administration of ENU or of the solvent (controls), the (101/El X C3H/El)F1 hybrid males were mated to untreated T-stock females. No enzyme-activity mutant was found in 3610 F1 offspring of the control group. After treatment of postspermatogonial germ-cell stages, 1 mutant in 1125 F1 offspring of males treated with 160 mg ENU/kg body weight, and 2 mutants in 1319 F1 offspring of a 250-mg/kg group were observed. After treatment of spermatogonia, 9 enzyme-activity mutants in 4247 F1 offspring of males treated with 80 mg ENU/kg body weight, 15 mutants in 3396 F1 offspring of a 160-mg/kg group, and 9 mutants in 1402 F1 offspring of a 250-mg/kg group were detected. The mutation frequencies in spermatogonia were significantly different from that of the controls (P less than 0.01). The dose-response curve was found to be linear. The frequencies of enzyme-activity mutations are comparable to those of recessive specific-locus mutations determined in the same experiments. Enzyme-activity mutants with reduced activity as well as mutants with enhanced activity were found. Genetic and biochemical characterization of enzyme-activity mutants was routinely performed. In inter se crossings of heterozygotes, no offspring expressing a third phenotype other than the wild type and the heterozygote were found in approximately half of the mutation studies. The recovered mouse mutants might be used as animal models to study corresponding genetic diseases in humans.

    Mutation research 1987;176;1;81-91

  • Genetic mapping of Pim-1 putative oncogene to mouse chromosome 17.

    Hilkens J, Cuypers HT, Selten G, Kroezen V, Hilgers J and Berns A

    Pim-1 is a putative oncogene activated in T-cell lymphomas induced by Moloney and AKR mink cell focus forming (MCF) viruses. We have determined the chromosomal localization of the Pim-1 gene in mice by Southern blot analysis of DNAs obtained from a panel of mouse-Chinese hamster somatic cell hybrids. The Pim-1 gene was localized on chromosome 17, a chromosome frequently aberrant in T-cell lymphomas. Two chromosomal regions, containing sequences homologous to regions within the Pim-1 locus, were localized on chromosome 6 and 16.

    Somatic cell and molecular genetics 1986;12;1;81-8

  • Chromosomal assignments of genes for trypsin, chymotrypsin B, and elastase in mouse.

    Honey NK, Sakaguchi AY, Lalley PA, Quinto C, MacDonald RJ, Craik C, Bell GI, Rutter WJ and Naylor SL

    The mouse genes for the serine proteases trypsin (Try-1), chymotrypsin B (Ctrb), and elastase (Ela-1) were chromosomally assigned using Southern blot hybridization of mouse X Chinese hamster cell hybrid DNA. cDNA probes for the three genes were hybridized to cell hybrid DNA cleaved with BamHI or HindIII and the segregation of Try-1, Ctrb, and Ela-1 was correlated with the segregation of mouse chromosomes. Try-1 is located on chromosome 6, Ctrb is on chromosome 8, and Ela-1 is on chromosome 15. The three genes fall into three syntenic groups that are conserved in the mouse and human genomes.

    Funded by: NIGMS NIH HHS: GM 20454

    Somatic cell and molecular genetics 1984;10;4;377-83

  • Genetic mapping in mammals: chromosome map of domestic cat.

    O'Brien SJ and Nash WG

    A genetic map of 31 biochemical loci located on 17 feline syntenic (linkage) groups has been derived by somatic cell genetic analysis of cat-rodent hybrids. Most of these syntenic groups have been assigned to one of the 19 feline chromosomes. Comparative linkage analysis of the feline biochemical loci and homologous human loci revealed considerable conservation of linkage associations between the primates and the Felidae (order Carnivora). Many of these same linkage groups have not been conserved in the murine genome. The genetic and evolutionary implications of comparative mapping analysis among mammalian species are discussed.

    Science (New York, N.Y.) 1982;216;4543;257-65

  • Assignment of a Mus musculus gene for triosephosphate isomerase to chromosome 6 and for glyoxalase-I to chromosome 17 using somatic cell hybrids.

    Minna JD, Bruns GA, Krinsky AH, Lalley PA, Francke U and Gerald PS

    Chinese hamster X mouse hybrid cells segregating mouse chromosomes have been used to assign a gene for triosephosphate isomerase (TPI-1, EC 5.3.1.1, McKusick No. 19045) to mouse chromosome 6, and a gene for Glyoxalase-I (GLO-1, EC 4.4.1.5, McKusick No 13875) to mouse chromosome 17. The genes for TPI-1 and lactate dehydrogenase B are syntenic in man and probably so in the dog. It is therefore likely that they are syntenic also in the mouse. It is of interest then that there is a mouse gene, Ldr-1, on chromosome 6 that regulates the level of LDH B subunits in mouse erythrocytes. The locus for GLO-1 is closely linked to the major histocompatibility complex in man. Since the major histocompatibility complex in the mouse is present on chromosome 17, this locus and the Glo-1 locus are syntenic in the mouse as well. This finding adds to the number of autosomal gene pairs which are syntenic in both mouse and man and reinforces the belief that there is considerable conservation. of linkage groups during evolution.

    Somatic cell genetics 1978;4;2;241-52

  • Assignment of the genes for triose phosphate isomerase to chromosome 6 and tripeptidase-1 to chromosome 10 in Mus musculus by somatic cell hybridization.

    Leinwand LA, Kozak CA and Ruddle FH

    Evidence is presented for the assignment of the gene for triose phosphate isomerase to Mus musculus chromosome 6 and tripeptidase-1 to chromosome 10 by synteny testing and chromosome assignment in Chinese hamster X mouse somatic cell hybrid clones. Neither TPI nor TRIP-1 were expressed concordantly with any known isozyme markers in 45 hybrid clones (13 primary and 32 secondary). Karyotypic analysis of 21 clones showed that the expression of TPI and chromosome 6 were concordant in all cases as was expressed of TRIP-1 and chromosome 10. Both chromosomes were previously unmarked by isozymes.

    Somatic cell genetics 1978;4;2;233-40

  • Assignment of the genes for thymidine kinase and galactokinase to Mus musculus chromosome 11 and the preferential segregation of this chromosome in Chinese hamster/mouse somatic cell hybrids.

    Kozak CA and Ruddle FH

    Somatic cell genetics 1977;3;2;121-33

Gene lists (8)

Gene List Source Species Name Description Gene count
L00000001 G2C Mus musculus Mouse PSD Mouse PSD adapted from Collins et al (2006) 1080
L00000003 G2C Mus musculus Mouse clathrin Mouse clathrin coated vesicle genes adapted from Collins et al (2006) 150
L00000004 G2C Mus musculus Mouse Synaptosome Mouse Synaptosome adapted from Collins et al (2006) 152
L00000007 G2C Mus musculus Mouse NRC Mouse NRC adapted from Collins et al (2006) 186
L00000008 G2C Mus musculus Mouse PSP Mouse PSP adapted from Collins et al (2006) 1121
L00000060 G2C Mus musculus BAYES-COLLINS-HUMAN-PSD-CONSENSUS Human cortex PSD consensus (ortho) 748
L00000070 G2C Mus musculus BAYES-COLLINS-HUMAN-PSD-FULL Human cortex biopsy PSD full list (ortho) 1461
L00000072 G2C Mus musculus BAYES-COLLINS-MOUSE-PSD-FULL Mouse cortex PSD full list 1556
© G2C 2014. The Genes to Cognition Programme received funding from The Wellcome Trust and the EU FP7 Framework Programmes:
EUROSPIN (FP7-HEALTH-241498), SynSys (FP7-HEALTH-242167) and GENCODYS (FP7-HEALTH-241995).

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