G2Cdb::Gene report

Gene id
G00003089
Gene symbol
Gls (MGI)
Species
Mus musculus
Description
glutaminase
Orthologue
G00006079 (Homo sapiens)

Databases (3)

Gene
ENSMUSG00000026103 (Ensembl mouse gene)
14660 (Entrez Gene)
Marker Symbol
MGI:95752 (MGI)

Literature (33)

Pubmed - other

  • Glutaminase-deficient mice display hippocampal hypoactivity, insensitivity to pro-psychotic drugs and potentiated latent inhibition: relevance to schizophrenia.

    Gaisler-Salomon I, Miller GM, Chuhma N, Lee S, Zhang H, Ghoddoussi F, Lewandowski N, Fairhurst S, Wang Y, Conjard-Duplany A, Masson J, Balsam P, Hen R, Arancio O, Galloway MP, Moore HM, Small SA and Rayport S

    Department of Psychiatry, Columbia University, New York, NY 10032, USA.

    Dysregulated glutamatergic neurotransmission has been strongly implicated in the pathophysiology of schizophrenia (SCZ). Recently, presynaptic modulation of glutamate transmission has been shown to have therapeutic promise. We asked whether genetic knockdown of glutaminase (gene GLS1) to reduce glutamatergic transmission presynaptically by slowing the recycling of glutamine to glutamate, would produce a phenotype relevant to SCZ and its treatment. GLS1 heterozygous (GLS1 het) mice showed about a 50% global reduction in glutaminase activity, and a modest reduction in glutamate levels in brain regions relevant to SCZ pathophysiology, but displayed neither general behavioral abnormalities nor SCZ-associated phenotypes. Functional imaging, measuring regional cerebral blood volume, showed hippocampal hypometabolism mainly in the CA1 subregion and subiculum, the inverse of recent clinical imaging findings in prodromal and SCZ patients. GLS1 het mice were less sensitive to the behavioral stimulating effects of amphetamine, showed a reduction in amphetamine-induced striatal dopamine release and in ketamine-induced frontal cortical activation, suggesting that GLS1 het mice are resistant to the effects of these pro-psychotic challenges. Moreover, GLS1 het mice showed clozapine-like potentiation of latent inhibition, suggesting that reduction in glutaminase has antipsychotic-like properties. These observations provide further support for the pivotal role of altered glutamatergic synaptic transmission in the pathophysiology of SCZ, and suggest that presynaptic modulation of the glutamine-glutamate pathway through glutaminase inhibition may provide a new direction for the pharmacotherapy of SCZ.

    Funded by: NIA NIH HHS: P50 AG008702, R01 AG025161; NIDA NIH HHS: K02 DA000356, R01 DA016373, R01 DA016736, R21 DA014055, T32 DA016224; NIMH NIH HHS: P50 MH066171, P50 MH066171-059001, R01 MH068073; NINDS NIH HHS: R01 NS049442

    Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 2009;34;10;2305-22

  • Necrotic neurons enhance microglial neurotoxicity through induction of glutaminase by a MyD88-dependent pathway.

    Pais TF, Figueiredo C, Peixoto R, Braz MH and Chatterjee S

    Instituto Gulbenkian de Ciência, Rua da Quinta Grande, 6, 2780-156 Oeiras, Portugal. tfariapais@gmail.com

    Background: Microglia are macrophage-like cells that constantly sense the microenvironment within the central nervous system (CNS). In the event of neuronal stress or injury, microglial cells rapidly react and change their phenotype. This response may lead to a deleterious type of microglial activation, which is often associated with neuroinflammation and neurotoxicity in several neuropathological conditions. We investigated the molecular mechanisms underlying triggering of microglial activation by necrotic neuronal damage.

    Methods: Primary cultures of microglia were used to study the effect of necrotic neurons on microglial inflammatory responses and toxicity towards cerebellar granule neurons (CGN). The mouse hippocampal cell line, HT22, was used in this study as the main source of necrotic neurons to stimulate microglia. To identify the signal transduction pathways activated in microglia, primary microglial cultures were obtained from mice deficient in Toll-like receptor (TLR) -2, -4, or in the TLR adapter protein MyD88.

    Results: Necrotic neurons, but not other necrotic cell types, induced microglial activation which was characterized by up-regulation of: i) MHC class II; ii) co-stimulatory molecules, i.e. CD40 and CD24; iii) beta2 integrin CD11b; iii) pro-inflammatory cytokines, i.e. interleukin 6 (IL-6), IL-12p40 and tumor-necrosis factor (TNF); iv) pro-inflammatory enzymes such as nitric oxide synthase (iNOS, type II NOS), indoleamine 2,3-dioxygenase (IDO) and cyclooxygenase-2 (COX-2) and increased microglial motility. Moreover, microglia-conditioned medium (MCM) obtained from cultures of activated microglia showed increased neurotoxicity mediated through the N-methyl-D-aspartate receptor (NMDAR). The activation of microglia by necrotic neurons was shown to be dependent on the TLR-associated adapter molecule myeloid differentiation primary response gene (MyD88). Furthermore, MyD88 mediated enhanced neurotoxicity by activated microglia through up-regulation of the expression and activity of glutaminase, an enzyme that produces glutamate, which is an NMDAR agonist.

    Conclusion: These results show that necrotic neurons activate in microglia a MyD88-dependent pathway responsible for a pro-inflammatory response that also leads to increased neurotoxic activity through induction of glutaminase. This finding contributes to better understanding the mechanisms causing increased neuroinflammation and microglial neurotoxicity in a neurodegenerative environment.

    Journal of neuroinflammation 2008;5;43

  • Origin of climbing fiber neurons and their developmental dependence on Ptf1a.

    Yamada M, Terao M, Terashima T, Fujiyama T, Kawaguchi Y, Nabeshima Y and Hoshino M

    Department of Pathology and Tumor Biology, Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto 606-8501, Japan.

    Climbing fiber (CF) neurons in the inferior olivary nucleus (ION) extend their axons to Purkinje cells, playing a crucial role in regulating cerebellar function. However, little is known about their precise place of birth and developmental molecular machinery. Here, we describe the origin of the CF neuron lineage and the involvement of Ptf1a (pancreatic transcription factor 1a) in CF neuron development. Ptf1a protein was found to be expressed in a discrete dorsolateral region of the embryonic caudal hindbrain neuroepithelium. Because expression of Ptf1a is not overlapping other transcription factors such as Math1 (mouse atonal homolog 1) and Neurogenin1, which are suggested to define domains within caudal hindbrain neuroepithelium (Landsberg et al., 2005), we named the neuroepithelial region the Ptf1a domain. Analysis of mice that express beta-galactosidase from the Ptf1a locus revealed that CF neurons are derived from the Ptf1a domain. In contrast, retrograde labeling of precerebellar neurons indicated that mossy fiber neurons are not derived from Ptf1a-expressing progenitors. We could observe a detailed migratory path of CF neurons from the Ptf1a domain to the ION during embryogenesis. In Ptf1a null mutants, putative immature CF neurons produced from this domain were unable to migrate or differentiate appropriately, resulting in a failure of ION formation. Apoptotic cells were observed in the mutant hindbrain. Furthermore, the fate of some cells in the Ptf1a lineage were changed to mossy fiber neurons in Ptf1a null mutants. These findings clarify the precise origin of CF neurons and suggest that Ptf1a controls their fate, survival, differentiation, and migration during development.

    The Journal of neuroscience : the official journal of the Society for Neuroscience 2007;27;41;10924-34

  • Mice lacking brain/kidney phosphate-activated glutaminase have impaired glutamatergic synaptic transmission, altered breathing, disorganized goal-directed behavior and die shortly after birth.

    Masson J, Darmon M, Conjard A, Chuhma N, Ropert N, Thoby-Brisson M, Foutz AS, Parrot S, Miller GM, Jorisch R, Polan J, Hamon M, Hen R and Rayport S

    Unité Mixte de Recherche U677, NeuroPsychoPharmacologie, Faculté de Médecine Pitié-Salpêtrière, 75634 Paris Cedex 13, France. jumasson@ext.jussieu.fr

    Neurotransmitter glutamate has been thought to derive mainly from glutamine via the action of glutaminase type 1 (GLS1). To address the importance of this pathway in glutamatergic transmission, we knocked out GLS1 in mice. The insertion of a STOP cassette by homologous recombination produced a null allele that blocked transcription, encoded no immunoreactive protein, and abolished GLS1 enzymatic activity. Null mutants were slightly smaller, were deficient in goal-directed behavior, hypoventilated, and died in the first postnatal day. No gross or microscopic defects were detected in peripheral organs or in the CNS. In cultured neurons from the null mutants, miniature EPSC amplitude and duration were normal; however, the amplitude of evoked EPSCs decayed more rapidly with sustained 10 Hz stimulation, consistent with an observed reduction in depolarization-evoked glutamate release. Because of this activity-dependent impairment in glutamatergic transmission, we surmised that respiratory networks, which require temporal summation of synaptic input, would be particularly affected. We found that the amplitude of inspirations was decreased in vivo, chemosensitivity to CO2 was severely altered, and the frequency of pacemaker activity recorded in the respiratory generator in the pre-Bötzinger complex, a glutamatergic brainstem network that can be isolated in vitro, was increased. Our results show that although alternate pathways to GLS1 glutamate synthesis support baseline glutamatergic transmission, the GLS1 pathway is essential for maintaining the function of active synapses, and thus the mutation is associated with impaired respiratory function, abnormal goal-directed behavior, and neonatal demise.

    Funded by: NIDA NIH HHS: DA00356, DA14055, K02 DA000356, K02 DA000356-01A2, K02 DA000356-02, K02 DA000356-03, K02 DA000356-04, K02 DA000356-05, K02 DA000356-06, R01 DA017978, R01 DA017978-01A2, R21 DA014055, R21 DA014055-01, R21 DA014055-02, R21 DA014055-03

    The Journal of neuroscience : the official journal of the Society for Neuroscience 2006;26;17;4660-71

  • BGEM: an in situ hybridization database of gene expression in the embryonic and adult mouse nervous system.

    Magdaleno S, Jensen P, Brumwell CL, Seal A, Lehman K, Asbury A, Cheung T, Cornelius T, Batten DM, Eden C, Norland SM, Rice DS, Dosooye N, Shakya S, Mehta P and Curran T

    Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, Tennessee, United States.

    Funded by: NINDS NIH HHS: 5R37NS036558, N01-NS-0-2331, R37 NS036558

    PLoS biology 2006;4;4;e86

  • Ptf1a, a bHLH transcriptional gene, defines GABAergic neuronal fates in cerebellum.

    Hoshino M, Nakamura S, Mori K, Kawauchi T, Terao M, Nishimura YV, Fukuda A, Fuse T, Matsuo N, Sone M, Watanabe M, Bito H, Terashima T, Wright CV, Kawaguchi Y, Nakao K and Nabeshima Y

    Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan. mikio@lmls.med.kyoto-u.ac.jp

    The molecular machinery governing glutamatergic-GABAergic neuronal subtype specification is unclear. Here we describe a cerebellar mutant, cerebelless, which lacks the entire cerebellar cortex in adults. The primary defect of the mutant brains was a specific inhibition of GABAergic neuron production from the cerebellar ventricular zone (VZ), resulting in secondary and complete loss of external germinal layer, pontine, and olivary nuclei during development. We identified the responsible gene, Ptf1a, whose expression was lost in the cerebellar VZ but was maintained in the pancreas in cerebelless. Lineage tracing revealed that two types of neural precursors exist in the cerebellar VZ: Ptf1a-expressing and -nonexpressing precursors, which generate GABAergic and glutamatergic neurons, respectively. Introduction of Ptf1a into glutamatergic neuron precursors in the dorsal telencephalon generated GABAergic neurons with representative morphological and migratory features. Our results suggest that Ptf1a is involved in driving neural precursors to differentiate into GABAergic neurons in the cerebellum.

    Neuron 2005;47;2;201-13

  • Prediction of the coding sequences of mouse homologues of KIAA gene: IV. The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs identified by screening of terminal sequences of cDNA clones randomly sampled from size-fractionated libraries.

    Okazaki N, F-Kikuno R, Ohara R, Inamoto S, Koseki H, Hiraoka S, Saga Y, Seino S, Nishimura M, Kaisho T, Hoshino K, Kitamura H, Nagase T, Ohara O and Koga H

    Kazusa DNA Research Institute, 2-6-7 Kazusa-Kamatari, Kisarazu, Chiba 292-0818, Japan.

    We have been conducting a mouse cDNA project to predict protein-coding sequences of mouse homologues of human KIAA and FLJ genes since 2001. As an extension of these projects, we herein present the entire sequences of 500 mKIAA cDNA clones and 4 novel cDNA clones that were incidentally identified during this project. We have isolated cDNA clones from the size-fractionated mouse cDNA libraries derived from 7 tissues and 3 types of cultured cells. The average size of the 504 cDNA sequences reached 4.3 kb and that of the deduced amino acid sequences from these cDNAs was 807 amino acid residues. We assigned the integrity of CDSs from the comparison with the corresponding human KIAA cDNA sequences. The comparison of mouse and human sequences revealed that two different human KIAA cDNAs are derived from single genes. Furthermore, 3 out of 4 proteins encoded in the novel cDNA clones showed moderate sequence similarity with human KIAA proteins, thus we could obtain new members of KIAA protein families through our mouse cDNA projects.

    DNA research : an international journal for rapid publication of reports on genes and genomes 2004;11;3;205-18

  • 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

  • Cloning and characterization of HARP/SMARCAL1: a prokaryotic HepA-related SNF2 helicase protein from human and mouse.

    Coleman MA, Eisen JA and Mohrenweiser HW

    Biology and Biotechnology Research Program, Lawrence Livermore National Laboratory, California 94551, USA. coleman16@llnl.gov

    The SNF2 gene family consists of a large group of proteins involved in transcriptional regulation, maintenance of chromosome integrity, and various aspects of DNA repair. We cloned a novel SNF2 family human cDNA, with sequence identity to the Escherichia coli RNA polymerase-binding protein HepA and named the human hepA-related protein (HHARP/SMARCAL1). In addition, the mouse ortholog (Mharp/Smarcal1) was cloned, and the Caenorhabditis elegans ortholog (CEHARP) was identified in the GenBank database. Phylogenetic analysis indicates that the HARP proteins share a high level of sequence similarity to the seven motif helicase core region (SNF2 domain) with identifiable orthologs in other eukaryotic species, except for yeast. Purified His-tagged HARP/SMARCAL1 protein exhibits single-stranded DNA-dependent ATPase activity, consistent with it being a member of the SNF2 family of proteins. Both the human and the mouse genes consist of 17 exons and 16 introns. The human gene maps to chromosome 2q34-q36, and the mouse gene is localized to the syntenic region of chromosome 1 (between markers Gls and Acrg). HARP/SMARCAL1 transcripts are ubiquitously expressed in human and mouse tissues, with testis presenting the highest levels of mRNA expression in humans.

    Genomics 2000;65;3;274-82

  • Identification and genetic mapping of differentially expressed genes in mice differing at the If1 interferon regulatory locus.

    Kozak CA, Su Y, Raj NB and Pitha PM

    Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, Building 4, Room 329, 4 Center Drive MSC 0460, Bethesda, Maryland 20982-0460, USA.

    A subtractive cDNA library was used to identify differentially expressed genes in mouse strains that differ at If1, a locus that regulates response to interferon induction by Newcastle Disease Virus infection. Among the isolated clones, sequence analysis identified the ribosomal proteins L37a and S8 as well as cDNAs for thymosine beta4, the QM transcriptional factor, and a novel genetic sequence. Analysis of two multilocus mouse crosses showed that the thymosine beta4 gene, Ptmb4, is present as a single-copy gene that maps to distal Chr X. The L37a, S8, and QM clones are all members of large multilocus families. These five clones were used to determine the map locations for 37 loci, of which 31 had not previously been described. The novel genetic sequence, D3Ppr1, mapped to distal Chr 3 near the position of the If1 locus, suggesting it may be a candidate for this regulatory gene.

    Funded by: NIAID NIH HHS: AI19737

    Mammalian genome : official journal of the International Mammalian Genome Society 1999;10;9;853-7

  • Physical and genetic linkage of glutaminase (Gls), signal transducer and activator of transcription 1 (Stat1), and xeroderma pigmentosum complementation group G (Xpg) on mouse proximal chromosome 1.

    Lévy N, Boettger-Tong H, Dohmae K, Agoulnik AI, Ty TI, Nishimune Y and Bishop CE

    Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, 77030, USA. nlevy@bcm.tmc.edu

    Genomics 1998;54;2;355-6

  • Genetic mapping of the mouse ferritin light chain gene and 11 pseudogenes on 11 mouse chromosomes.

    Filie JD, Buckler CE and Kozak CA

    Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-0460, USA.

    We typed the progeny of two sets of genetic crosses to determine the map locations for loci containing sequences related to the ferritin light chain (Ft11) gene. Twelve loci were positioned on 11 different chromosomes. One of these genes mapped to a position on Chr 7 predicted to contain the expressed gene on the basis of the previously determined position of the human homolog on 19q13.3-q13.4.

    Mammalian genome : official journal of the International Mammalian Genome Society 1998;9;2;111-3

  • Analysis of glutaminase activity and RNA expression in preimplantation mouse embryos.

    Chatot CL, Lawry JR, Germain B and Ziomek CA

    Department of Biology, Ball State University, Muncie, Indiana, USA.

    Glutamine is utilized as an energy substrate in preimplantation mouse embryos. Glutaminase is the enzyme responsible for the conversion of glutamine to glutamic acid, which then enters the trichloro acetic acid (TCA) cycle as alpha-ketoglutarate. Glutaminase enzyme activity was assessed in preimplantation embryos that developed in vivo, and glutaminase RNA expression was examined in embryos that developed in vivo or were cultured in CZB medium to various preimplantation stages between 1-cell and blastocyst. Glutaminase activity in 1-8-cell-stage mouse embryos that developed in vivo ranged from 0.009-0.01 U/mg protein (2.39-2.95 x 10(-7) U per embryo) and increased 3-4 fold to 0.034 U/mg protein (8.13 x 10(-7) U per embryo) at the blastocyst stage. Relative stage-specific expression of glutaminase RNA was assessed by reverse transcription polymerase chain reaction (RT-PCR) in embryos that developed both in vivo and in CZB culture. In vivo, glutaminase RNA was expressed at the 1-cell stage, declined to 23% of 1-cell levels at the early 2-cell stage, and reaccumulated from late 2-cell through blastocyst stage, where it reached a high of 204% of 1-cell levels. CZB-cultured embryos exhibited a similar pattern of developmental RNA expression, declining to 30% of 1-cell levels at the early 2-cell stage, and increasing RNA expression at the blastocyst stage to 191% of the 1-cell level.

    Funded by: NCI NIH HHS: P30CA12708; NICHD NIH HHS: HD21942, HD30436

    Molecular reproduction and development 1997;47;3;248-54

  • FISH mapping of three ammonia metabolism genes (Glul, Cps1, Glud1) in rat, and the chromosomal localization of GLUL in human and Cps1 in mouse.

    Helou K, Das AT, Lamers WH, Hoovers JM, Szpirer C, Szpirer J, Klinga-Levan K and Levan G

    Department of Genetics, Göteborg University Medicinareg. 9C, S-413 90 Göteborg, Sweden.

    Mammalian genome : official journal of the International Mammalian Genome Society 1997;8;5;362-4

  • The Nab2 and Stat6 genes share a common transcription termination region.

    Svaren J, Apel ED, Simburger KS, Jenkins NA, Gilbert DJ, Copeland NA and Milbrandt J

    Department of Pathology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.

    The two Nab genes, coding for transcriptional corepressors of NGFI-A (Egr-1, Krox24, zif268) and Krox20, have been localized to two regions of the genome, each of which contains at least two members of the Stat gene family. The association of the two Nab genes with the Stat clusters on mouse chromosomes 1 and 10 (human chromosomes 2 and 12) suggest that a Nab gene was involved in at least one of the duplication events that resulted in dispersion of the primordial Stat gene pair to three different mouse chromosomes. Sequencing of the Nab2 genomic locus revealed that it is situated very close to the Stat6 gene. The transcripts of the two genes converge, such that the 3' ends of the Stat6 and Nab2 mRNAs overlap by 58 bp. Both transcripts terminate within a 78-bp region that is absolutely conserved between mouse and human. Analysis of Nab2 cDNA revealed that there is an alternatively spliced form of the Nab2 transcript (lacking exon 3) that produces a protein that lacks the ability to repress transcription by NGFI-A and Krox20.

    Funded by: NCI NIH HHS: P01 CA49712; NIGMS NIH HHS: 1F32GM18058-01

    Genomics 1997;41;1;33-9

  • Mapping of unconventional myosins in mouse and human.

    Hasson T, Skowron JF, Gilbert DJ, Avraham KB, Perry WL, Bement WM, Anderson BL, Sherr EH, Chen ZY, Greene LA, Ward DC, Corey DP, Mooseker MS, Copeland NG and Jenkins NA

    Department of Biology, Yale University, New Haven, Connecticut 06520, USA.

    Myosins are molecular motors that move along filamentous actin. Seven classes of myosin are expressed in vertebrates: conventional myosin, or myosin-II, as well as the 6 unconventional myosin classes-I, -V, -VI, -VII, -IX, and -X. We have mapped in mouse 22 probes encompassing all known unconventional myosins and, as a result, have identified 16 potential unconventional myosin genes. These genes include 7 myosins-I, 2 myosins-V, 1 myosin-VI, 3 myosins-VII, 2 myosins-IX, and 1 myosin-X. The map location of 5 of these genes was identified in human chromosomes by fluorescence in situ hybridization.

    Funded by: NIDDK NIH HHS: DK25387, DK38979; NINDS NIH HHS: NS33689

    Genomics 1996;36;3;431-9

  • Genetic mapping of the human and mouse phospholipase C genes.

    Lyu MS, Park DJ, Rhee SG and Kozak CA

    Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.

    To determine chromosome positions for 10 mouse phospholipase C (PLC) genes, we typed the progeny of two sets of genetic crosses for inheritance of restriction enzyme polymorphisms of each PLC. Four mouse chromosomes, Chr 1, 11, 12, and 19, contained single PLC genes. Four PLC loci, Plcb1, Plcb2, Plcb4, and Plcg1, mapped to three sites on distal mouse Chr 2. Two PLC genes, Plcd1 and Plcg2, mapped to distinct sites on Chr 8. We mapped the human homologs of eight of these genes to six chromosomes by analysis of human x rodent somatic cell hybrids. The map locations of seven of these genes were consistent with previously defined regions of conserved synteny; Plcd1 defines a new region of homology between human Chr 3 and mouse Chr 8.

    Mammalian genome : official journal of the International Mammalian Genome Society 1996;7;7;501-4

  • Dispersion of chromogranin/secretogranin secretory protein family loci in mammalian genomes.

    Mahata SK, Kozak CA, Szpirer J, Szpirer C, Modi WS, Gerdes HH, Huttner WB and O'Connor DT

    Department of Medicine, University of California, San Diego, California, 92161, USA.

    Chromogranin A, chromogranin B, and secretogranin II, members of the chromogranin/secretogranin secretory protein family, are overexpressed in some human hereditary maladies and may have arisen, in part, from common ancestor genes. To understand better the mammalian chromosomal dispersion of this gene family and to facilitate studies of these genes in human illnesses and their animal models, we positioned the locus of each member in the rat, mouse, and human genomes. Our results indicate that each locus lies in a region of locally syntenic chromosomal homology across the three species.

    Genomics 1996;33;1;135-9

  • A large family of putative transmembrane receptors homologous to the product of the Drosophila tissue polarity gene frizzled.

    Wang Y, Macke JP, Abella BS, Andreasson K, Worley P, Gilbert DJ, Copeland NG, Jenkins NA and Nathans J

    Department of Molecular Biology, Howard Hughes Medical Institute, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.

    In Drosophila melanogaster, the frizzled gene plays an essential role in the development of tissue polarity as assessed by the orientation of cuticular structures. Through a combination of random cDNA sequencing, degenerate polymerase chain reaction amplification, and low stringency hybridization we have identified six novel frizzled homologues from mammals, at least 11 from zebrafish, several from chicken and sea urchin, and one from Caenorhabditis elegans. The complete deduced amino acid sequences of the mammalian and nematode homologues share with the Drosophila frizzled protein a conserved amino-terminal cysteine-rich domain and seven putative transmembrane segments. Each of the mammalian homologues is expressed in a distinctive set of tissues in the adult, and at least three are expressed during embryogenesis. As hypothesized for the Drosophila frizzled protein, the frizzled homologues are likely to act as transmembrane receptors for as yet unidentified ligands. These observations predict the existence of a family of signal transduction pathways that are homologous to the pathway that determines tissue polarity in Drosophila.

    The Journal of biological chemistry 1996;271;8;4468-76

  • Mouse chromosomal location of four Na/H exchanger isoform genes.

    Pathak BG, Shull GE, Jenkins NA and Copeland NG

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

    The Na/H exchanger genes Slc9a1, Slc9a2, Slc9a3, and Slc9a4 have been mapped in the mouse using an interspecific backcross panel. These loci map to previously defined homologous regions between human and mouse chromosomes and provide additional information regarding human/mouse comparative mapping.

    Funded by: NCI NIH HHS: N01-CO46000; NHLBI NIH HHS: HL 41496

    Genomics 1996;31;2;261-3

  • Report and abstracts of the Fourth International Workshop on Human Chromosome 2 Mapping 1996.

    Spur NK, Bashir R, Bushby K, Cox A, Cox S, Hilde Brandt F, Hill N, Kao FT, Krols L, Marzella R, Miller N, Nothwang HG, Rocchi M, Sarfarazi M, Stratakis CA, Wallgren-Petterson C and Naylor S

    Cytogenetics and cell genetics 1996;73;4;255-73

  • RNA expression and chromosomal location of the mouse long-chain acyl-CoA dehydrogenase gene.

    Hinsdale ME, Farmer SC, Johnson KR, Davisson MT, Hamm DA, Tolwani RJ and Wood PA

    Department of Comparative Medicine, School of Medicine, University of Alabama at Birmingham 35294-0019, USA.

    The cDNA for mouse long-chain acyl-CoA dehydrogenase (Acadl, gene symbol; LCAD, enzyme) was cloned and characterized. The cDNA was obtained by library screening and reverse transcription-polymerase chain reaction (RT-PCR). The deduced amino acid sequence showed a high degree of homology to both the rat and the human LCAD sequence. Northern analysis of multiple tissues using the mouse Acadl cDNA as a probe showed two bands in all tissues examined. We found a total of three distinct mRNAs for Acadl. These three mRNAs were encoded by a single gene that we mapped to mouse chromosome 1. The three transcripts differed in the 3' untranslated region due to use of alternative polyadenylation sites. Quantitative evaluation of a multitissue Northern blot showed a varied ratio of the larger transcript as compared with the smaller transcripts.

    Funded by: NCRR NIH HHS: RR01183, RR02599; NIGMS NIH HHS: GM46697; ...

    Genomics 1995;28;2;163-70

  • Stat4, a novel gamma interferon activation site-binding protein expressed in early myeloid differentiation.

    Yamamoto K, Quelle FW, Thierfelder WE, Kreider BL, Gilbert DJ, Jenkins NA, Copeland NG, Silvennoinen O and Ihle JN

    Department of Biochemistry, St. Jude Children's Research Hospital, Memphis, Tennessee 38105.

    Interferon regulation of gene expression is dependent on the tyrosine phosphorylation and activation of the DNA-binding activity of two related proteins of 91 kDa (STAT1) and/or 113 kDa (STAT2). Recent studies have suggested that these proteins are substrates of Janus kinases and that proteins related in STAT1 are involved in a number of signalling pathways, including those activated in myeloid cells by erythropoietin and interleukin-3 (IL-3). To clone STAT-related proteins from myeloid cells, degenerate oligonucleotides were used in PCRs to identify novel family members expressed in myeloid cells. This approach allowed the identification and cloning of the Stat4 gene, which is 52% identical to STAT1. Unlike STAT1, Stat4 expression is restricted but includes myeloid cells and spermatogonia. In the erythroid lineage, Stat4 expression is differentially regulated during differentiation. Functionally, Stat4 has the properties of other STAT family genes. In particular, cotransfection of expression constructs for Stat4 and Jak1 and Jak2 results in the tyrosine phosphorylation of Stat4 and the acquisition of the ability to bind to the gamma interferon (IFN-gamma)-activated sequence of the interferon regulatory factor 1 (IRF-1) gene. Stat4 is located on mouse chromosome 1 and is tightly linked to the Stat1 gene, suggesting that the genes arose by gene duplication. Unlike Stat1, neither IFN-alpha nor IFN-gamma activates Stat4. Nor is Stat4 activated in myeloid cells by a number of cytokines, including erythropoietin, IL-3, granulocyte colony-stimulating factor, stem cell factor, colon-stimulating factor 1, hepatocyte growth factor, IL-2, IL-4, and IL-6.

    Funded by: NCI NIH HHS: N01 CO-74101, P30 CA21765; NIDDK NIH HHS: R01 DK42932

    Molecular and cellular biology 1994;14;7;4342-9

  • Murine chromosomal location of the mu and kappa opioid receptor genes.

    Kozak CA, Filie J, Adamson MC, Chen Y and Yu L

    Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892.

    Opioid receptors are the membrane proteins that mediate the pain-relieving effect of opioid drugs, such as morphine and fentanyl as well as endogenous opioid peptides enkephalins and endorphins. Using cDNAs for the mu and the kappa opioid receptors, we mapped the chromosomal locations of their genes in mouse. Multilocus cross analysis located the mu receptor gene Oprm on Chr 10 and the kappa receptor gene Oprk1 on Chr 1. Both genes are near centromere, with no markers more centromeric. These data indicate that the two opioid receptors are different gene products, ruling out the possibility that they may be differential splicing products from the same gene.

    Funded by: NINDS NIH HHS: NS01557, NS28190

    Genomics 1994;21;3;659-61

  • Mouse thioredoxin gene maps on chromosome 4, whereas its pseudogene maps on chromosome 1.

    Taketo M, Matsui M, Rochelle JM, Yodoi J and Seldin MF

    Banyu Tsukuba Research Institute (Merck), Japan.

    Thioredoxins are involved in various biochemical systems and mediate both redox and nonredox functions. In mammalian cells, thioredoxin functions as an endogenous glucocorticoid receptor activating factor and as an adult T-cell leukemia-derived factor (ADF) that stimulates expression of interleukin-2 receptor in human T-cell leukemia virus (HTLV)-I transformed T cells. We have mapped the thioredoxin gene (Txn) and its processed pseudogene (Txn-ps1) in the mouse using a panel of interspecific backcross mice. Txn maps to Chr 4, whereas Txn-ps1 maps to the proximal region of Chr 1.

    Funded by: NHGRI NIH HHS: HG00734

    Genomics 1994;21;1;251-3

  • Physical and linkage mapping of the human and murine genes for the alpha 1 chain of type IX collagen (COL9A1).

    Warman ML, Tiller GE, Polumbo PA, Seldin MF, Rochelle JM, Knoll JH, Cheng SD and Olsen BR

    Department of Anatomy and Cellular Biology, Harvard Medical School, Boston, Massachusetts 02115.

    Type IX collagen, a member of the FACIT family of extracellular matrix proteins, is a heterotrimer composed of three genetically distinct alpha chains. The cDNAs for the human and mouse alpha 1 (IX) chains have been cloned. In this paper we confirm the mapping of the human COL9A1 gene to chromosome 6q12-q13 by fluorescence in situ hybridization utilizing two genomic clones which also contain short tandem repeat polymorphisms. We also report the characterization of these repeats and their incorporation into the chromosome 6 linkage map. The COL9A1 locus shows no recombination with the marker D6Z1 (Z = 27.61 at theta = O) and identifies the most likely locus order of KRAS1P-[D6Z1-COL9A1]-D6S30. In addition, using an interspecific backcross panel, we have mapped murine Col9a1 to mouse chromosome 1. Together with other comparative mapping results, these data suggest that the pericentric region of human chromosome 6 is homologous to the most proximal segment of mouse chromosome 1. These data may facilitate linkage studies with COL9A1 (or Col9a1) as a candidate gene for hereditary chondrodysplasias and osteoarthritis.

    Funded by: NIAMS NIH HHS: AR 36819, AR 36820; NICHD NIH HHS: 1P30HD28819; ...

    Genomics 1993;17;3;694-8

  • Identification and genetic mapping of the murine gene and 20 related sequences encoding chromosomal protein HMG-17.

    Johnson KR, Cook SA, Ward-Bailey P, Bustin M and Davisson MT

    Jackson Laboratory, Bar Harbor, Maine 04609.

    HMG-17 is an abundant, nonhistone chromosomal protein that binds preferentially to nucleosomal core particles of mammalian chromatin. The human gene for HMG-17 has been localized to Chromosome (Chr) 1p, but the murine gene has not been previously mapped. Here we identify the murine functional gene, Hmg17, from among more than 25 related sequences (probably processed pseudogenes) and show that it is located on mouse Chr 4, in a region known to have conserved linkage relationships with human Chr 1p. We also report the map locations of 20 additional Hmg17-related sequences on mouse Chrs 1, 2, 3, 5, 7, 8, 9, 13, 15, 16, 17, 18, and X. The multiple, dispersed members of the Hmg17 multigene family can be detected efficiently with a single cDNA probe and provide useful markers for genetic mapping studies in mice.

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

    Mammalian genome : official journal of the International Mammalian Genome Society 1993;4;2;83-9

  • Localization of growth arrest-specific genes on mouse chromosomes 1, 7, 8, 11, 13, and 16.

    Colombo MP, Martinotti A, Howard TA, Schneider C, D'Eustachio P and Seldin MF

    Division of Experimental Oncology D, Istituto Nazionali Tumori, Milano, Italy.

    Growth arrest in NIH3T3 cells is associated with increased expression of a variety of mRNAs, several of which have been isolated as cDNA clones. Six of these growth arrest-specific (Gas) genes were mapped by following the inheritance of DNA restriction fragment length variants (RFLVs) associated with them in panels of recombinant inbred (RI) strains of mice and in the progeny of backcrosses both between laboratory mouse strains and between a laboratory strain and Mus spretus. The six genes are unlinked. Gas-1 maps to Chromosome (Chr) 13, Gas-2 to Chr 7, Gas-3 to Chr 11, Gas-4 to Chr 16, Gas-6 to Chr 8, and Gas-10 to Chr 1.

    Funded by: NHGRI NIH HHS: HG00101

    Mammalian genome : official journal of the International Mammalian Genome Society 1992;2;2;130-4

  • 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

  • Cd28 and Ctla-4, two related members of the Ig supergene family, are tightly linked on proximal mouse chromosome 1.

    Howard TA, Rochelle JM and Seldin MF

    Department of Medicine, Duke University Medical Center, Durham, NC 27705.

    Funded by: NHGRI NIH HHS: HG-00101

    Immunogenetics 1991;33;1;74-6

  • Chromosomal assignments of 23 biochemical loci of the rat by using rat x mouse somatic cell hybrids.

    Yasue M, Serikawa T and Yamada J

    Institute of Laboratory Animals, Faculty of Medicine, Kyoto University, Japan.

    A panel of 18 rat x mouse somatic cell hybrid clones segregating individual rat chromosomes in different combinations was used to assign 23 biochemical loci to rat chromosomes. The chromosomal locations for these 23 loci were determined as follows: GOT1 on rat chromosome 1; HAGH on 2; ACP2, ADA, GANC, ITPA, and SORD on 3; LDHB on 4; PEPB on 7; GLB1 and HEXA on 8; IDH1 on 9; UMPH2 on 10; GUSB on 12; FH and PEPC on 13; PEPS on 14; ESD and NP on 15; DIA4 on 19; and PP on 20. In addition, ACP1 and GLO1 were reassigned to rat chromosomes 6 and 20, respectively. The chromosomal assignments of these loci extends the known syntenic homologies among rats, mice, and humans.

    Cytogenetics and cell genetics 1991;57;2-3;142-8

  • A glutaminase (gis) gene maps to mouse chromosome 1, rat chromosome 9, and human chromosome 2.

    Mock B, Kozak C, Seldin MF, Ruff N, D'Hoostelaere L, Szpirer C, Levan G, Seuanez H, O'Brien S and Banner C

    Laboratory of Genetics, NCI, Bethesda, Maryland 20892.

    A rat cDNA clone encoding a portion of phosphate-activated glutaminase was used to identify DNA restriction fragment length polymorphisms (RFLPs) in sets of somatic cell hybrids and between wild-derived and inbred strains of mice. Segregation of rat and mouse chromosomes among somatic cell hybrids indicated assignment to rat chromosome 9 and mouse chromosome 1. Analysis of chromosome 1 alleles for several genes in an interspecific cross between Mus spretus and C3H/HeJ-gld/gld mice indicates that glutaminase can be positioned within 5.5 +/- 2.0 cM proximal to Ctla-4. Similarly, human-hamster somatic cell hybrids were examined for RFLPs, and four human EcoRI restriction fragments were found to hybridize with the rat glutaminase probe. Two of these restriction fragments cosegregated and mapped to human chromosome 2 in a region that is syntenic with mouse chromosome 1 and rat chromosome 9.

    Genomics 1989;5;2;291-7

  • Genetic regulation of GM2 (NeuGc) expression in liver of mouse.

    Suzuki A, Hashimoto Y, Abe M, Kiuchi Y and Yamakawa T

    GM2 containing NeuGc was a major ganglioside in mouse liver of inbred strains such as DBA/2, BALB/c, C57BL/10 and C3H/He, which are commonly used for biochemical and immunological studies. On the other hand, the liver of WHT/Ht, an inbred strain, contained GM3 (NeuGc) as a major ganglioside and lacked GM2 (NeuGc). We report here that the GM2 (NeuGc) expression was analyzed in the liver of the progeny between WHT/Ht and DBA/2 and the positive expression of GM2 (NeuGc) was proved to be a dominant trait regulated by an autosomal single gene. Moreover, the N-acetylgalactosaminyltransferase activity to convert GM3 (NeuGc) to GM2 (NeuGc) was measured in the liver microsomal fraction of WHT/Ht, BALB/c and their F1. F1 expressed almost half of the activity in BALB/c and WHT/Ht did not express a detectable amount of activity. The backcross of F1 to WHT/Ht segregated into two groups. One expressed both GM2 (NeuGc) and the transferase activity and the other expressed neither of them. There was no exceptional individual which was not grouped into either of these two groups. These results indicate that GM2 (NeuGc) expression is directly regulated by the N -acetylgalactosaminyltregated into two groups. One expressed both GM2 (NeuGc) and the transferase activity and the other expressed neither of them. There was no exceptional individual which was not grouped into either of these two groups. These results indicate that GM2 (NeuGc) expression is directly regulated by the N-acetylgalactosaminyltransferase activity, the expression of the enzyme activity is regulated by an autosomal single gene and WHT/Ht is a mutant of the recessive homozygote which cannot express the enzyme activity in its liver. WHT/Ht does not develop any neurological symptoms but grows and breeds well. The brain ganglioside composition was proved to be identical to those in BALB/c brain. The result suggests that WHT/Ht has N-acetylgalactosaminyltransferase to convert GM3 (NeuAc) to GM2 (NeuAc) in its brain. It is a subject for further study to elucidate what kind of defect is involved in the GM2 (NeuGc) biosynthesis of WHT/Ht liver.

    Advances in experimental medicine and biology 1984;174;263-72

Gene lists (2)

Gene List Source Species Name Description Gene count
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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