G2Cdb::Gene report

Gene id
G00000402
Gene symbol
Dpysl5 (MGI)
Species
Mus musculus
Description
dihydropyrimidinase-like 5
Orthologue
G00001651 (Homo sapiens)

Databases (8)

Curated Gene
OTTMUSG00000022301 (Vega mouse gene)
Gene
ENSMUSG00000029168 (Ensembl mouse gene)
65254 (Entrez Gene)
742 (G2Cdb plasticity & disease)
Gene Expression
NM_023047 (Allen Brain Atlas)
Literature
608383 (OMIM)
Marker Symbol
MGI:1929772 (MGI)
Protein Sequence
Q9EQF6 (UniProt)

Synonyms (3)

  • CRAM
  • CRMP-5
  • Crmp5

Literature (14)

Pubmed - other

  • CRMP5 (collapsin response mediator protein 5) regulates dendritic development and synaptic plasticity in the cerebellar Purkinje cells.

    Yamashita N, Mosinger B, Roy A, Miyazaki M, Ugajin K, Nakamura F, Sasaki Y, Yamaguchi K, Kolattukudy P and Goshima Y

    Department of Molecular Pharmacology and Neurobiology, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan.

    Collapsin response mediator protein 5 (CRMP5) is one of the CRMP members that expresses abundantly in the developing brain. To examine the in vivo function of CRMP5, we generated crmp5-deficient (crmp5(-/-)) mice. Anti-calbindin immunofluorescence studies of crmp5(-/-) mice revealed aberrant dendrite morphology; specifically, a decrease in the size of soma and diameter of primary dendrite of the cerebellar Purkinje cells at postnatal day 21 (P21) and P28, but not at P14. Coincidentally, CRMP5 is detected in Purkinje cells at P21 and P28 from crmp5(+/-) mice. In cerebellar slices of crmp5(-/-) mice, the induction of long-term depression of excitatory synaptic transmission between parallel fibers and Purkinje cells was deficient. Given that brain-derived neurotrophic factor (BDNF) plays major roles in dendritic development, we tried to elucidate the possible roles of CRMP5 in BDNF signaling. The effect of BDNF to induce dendritic branching was markedly attenuated in cultured crmp5(-/-) neurons. Furthermore, CRMP5 was tyrosine phosphorylated when coexpressed with neurotrophic tyrosine kinase receptor type 2 (TrkB), a receptor for BDNF, in HEK293T cells. These findings suggest that CRMP5 is involved in the development, maintenance and synaptic plasticity of Purkinje cells.

    The Journal of neuroscience : the official journal of the Society for Neuroscience 2011;31;5;1773-9

  • 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

  • CRMP5 interacts with tubulin to inhibit neurite outgrowth, thereby modulating the function of CRMP2.

    Brot S, Rogemond V, Perrot V, Chounlamountri N, Auger C, Honnorat J and Moradi-Améli M

    Inserm, Unité 842, Université de Lyon, Lyon 1, Unité Mixte de Recherche S842, F-69372 Lyon Cedex 08, France.

    Collapsin response mediator proteins (CRMPs) are involved in signaling of axon guidance and neurite outgrowth during neural development and regeneration. Among these, CRMP2 has been identified as an important actor in neuronal polarity and axon outgrowth, these activities being correlated with the reorganization of cytoskeletal proteins. In contrast, the function of CRMP5, expressed during brain development, remains obscure. Here, we find that, in contrast to CRMP2, CRMP5 inhibits tubulin polymerization and neurite outgrowth. Knockdown of CRMP5 expression by small interfering RNA confirms its inhibitory functions. CRMP5 forms a ternary complex with MAP2 and tubulin, the latter involving residues 475-522 of CRMP5, exposed at the molecule surface. Using different truncated CRMP5 constructs, we demonstrate that inhibition of neurite outgrowth by CRMP5 is mediated by tubulin binding. When both CRMP5 and CRMP2 are overexpressed, the inhibitory effect of CRMP5 abrogates neurite outgrowth promotion induced by CRMP2, suggesting that CRMP5 acts as a dominant signal. In cultured hippocampal neurons, CRMP5 shows no effect on axon growth, whereas it inhibits dendrite outgrowth and formation, at an early developmental stage, correlated with its strong expression in neurites. At later stages, when dendrites begin to extend, CRMP5 expression is absent. However, CRMP2 is constantly expressed. Overexpression of CRMP5 with CRMP2 inhibits CRMP2-induced outgrowth both on the axonal and dendritic levels. Deficiency of CRMP5 expression enhanced the CRMP2 effect. This antagonizing effect of CRMP5 is exerted through a tubulin-based mechanism. Thus, the CRMP5 binding to tubulin modulates CRMP2 regulation of neurite outgrowth and neuronal polarity during brain development.

    The Journal of neuroscience : the official journal of the Society for Neuroscience 2010;30;32;10639-54

  • Proteomic analysis of neonatal mouse brain: evidence for hypoxia- and ischemia-induced dephosphorylation of collapsin response mediator proteins.

    Zhou Y, Bhatia I, Cai Z, He QY, Cheung PT and Chiu JF

    Department of Anatomy, The University of Hong Kong, Hong Kong.

    Perinatal hypoxia and ischemia (HI) are a significant cause of mortality and morbidity. To understand the molecular mechanisms for HI-induced brain damage, here we used a proteomic approach to analyze the alteration and modification of proteins in neonatal mouse brain 24 h after HI treatment. Significant changes of collapsin response mediator proteins (CRMPs) were observed in HI brain. CRMPs are a family of cytosolic proteins involved in axonal guidance and neuronal outgrowth. We found that CRMP2, CRMP4 and CRMP5 proteins were altered post-translationally after HI treatment. Mass spectrometric and Western blot analyses detected hypophosphorylated CRMP proteins after HI. Further analysis of CRMP kinases indicated inactivation of cyclin dependent kinase 5 (CDK5), a priming kinase of CRMPs and a neuronal specific kinase that plays pivotal roles in neuronal development and survival. The reduction of CDK5 activity was associated with underexpression of its activator p35. Taken together, our findings reveal HI-induced dephosphorylation of CRMPs in neonatal brain and suggest a novel mechanism for this modification. Hypophosphorylated CRMPs might be implicated in the pathogenesis of HI-related neurological disorders.

    Journal of proteome research 2008;7;6;2507-15

  • Localization of CRMP5 mRNA by in situ hybridisation during development of the mouse forebrain.

    McLaughlin D, Vidaki M and Karagogeos D

    University College Dublin, School of Biomolecular and Biomedical Sciences, Conway Institute, Belfield, Dublin 4, Ireland. davidmclaughlin@ucd.ie

    The expression of the collapse response mediator protein CRMP5 in the prenatal mouse is largely unknown. Evidence suggests that CRMP family members play important roles in neurite outgrowth, and CRMP5 is known to modulate outgrowth of processes in oligodendrocytes through signalling via neuropilin-1 and SemaA. Furthermore, CRMP family members function in axon regeneration after injury and are implicated in the early stages of Alzheimer's disease. Despite these findings relatively little is known about the specific roles these proteins play. The aim of the present study was to evaluate CRMP5 expression in the developing mouse forebrain using in situ hybridisation. Serial coronal sections of brain from E12.5 to E18.5 were analysed. We found highly specific patterns of expression which were restricted to the post-mitotic layers of both the ganglionic eminence and neocortex, and an additional domain of strong expression in the pyramidal layers of the hippocampus in all prenatal ages. Our results are therefore consistent with a role for CRMP5 in process extension. Interestingly, our results also revealed a temporal switch in high-expression levels from the ganglionic eminence to the cortex at a critical time during tangential cell migration. However, the pattern of expression appeared more representative of a general permissiveness for neurite outgrowth rather than one which is restricted to a particular cell subset or cell class. Additionally, expression was also found during periods predominated by neurogenesis and not neurite extension. We conclude that expression of CRMP5 is consistent with a dynamic implicit role in forebrain development.

    Neuroscience letters 2008;432;2;117-20

  • Identification of molecules preferentially expressed beneath the marginal zone in the developing cerebral cortex.

    Tachikawa K, Sasaki S, Maeda T and Nakajima K

    Department of Anatomy, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.

    During cerebral cortical development, the majority of excitatory neurons are born near the ventricle and migrate radially toward the marginal zone (MZ). Since the cells invariably stop migrating beneath the MZ, neurons are aligned in an "inside-out" manner in the cortical plate (CP); that is, the early-born and late-born neurons are ultimately positioned in the deep and superficial layers, respectively. Since dramatic morphological changes occur in cells beneath the MZ, several events critical for proper neuronal maturation and layer formation must take place. In this study, we screened for molecules strongly expressed beneath the MZ, and identified 28 genes that are preferentially expressed in the upper half of the mouse CP on both embryonic day (E) 16.5 and E18.5. Expression analyses in reeler and yotari mice, in which neurons terminate migration throughout the CP, suggested that these genes were indeed related to the events beneath the MZ rather than unrelatedly induced by the structures near the brain surface. Pathway analyses suggested calcium signaling to have an important role in cells beneath the MZ. The gene list presented here will be useful for clarifying the molecular mechanisms that control cortical development.

    Neuroscience research 2008;60;2;135-46

  • 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

  • Differential expression of CRMP1, CRMP2A, CRMP2B, and CRMP5 in axons or dendrites of distinct neurons in the mouse brain.

    Bretin S, Reibel S, Charrier E, Maus-Moatti M, Auvergnon N, Thevenoux A, Glowinski J, Rogemond V, Prémont J, Honnorat J and Gauchy C

    Institut National de la Santé et de la Recherche Médicale U114, Collège de France, 75231 Paris, France. christian.gauchy@college-de-france.fr

    CRMP1, CRMP2, and CRMP5 have been identified as cytosolic proteins relaying semaphorin 3A signalling, one of the molecular cues conducting axon and dendrite growth and guidance. They are highly expressed during brain ontogenesis, but, because of their lower levels in the adult, their distribution in the mature brain is poorly documented. By using specific antibodies, we investigated the cellular distribution of these CRMPs in different adult brain structures and in neural cell cultures with a special focus on the splice variants CRMP2A and CRMP2B. In brain sections of adult mouse, CRMP1, CRMP2B, and CRMP5 were located predominantly in dendrites of specific neuronal populations, such as cortical pyramidal neurons, hippocampal CA1 pyramidal cells, or Purkinje cerebellar cells. On the contrary, CRMP2A was specifically associated with axons of the corpus callosum, bundles of the striatum, and mossy fibers of the hippocampus. In cultures of cortical neurons, CRMP1, CRMP2A, CRMP2B, and CRMP5 were equally distributed throughout cell bodies, axons, or dendrites of neurons, whereas CRMP2A and CRMP5 were completely absent from Purkinje cerebellar cells in 12-day-old animals. By comparison, oligodendrocytes exclusively express CRMP2B and CRMP5 in cell bodies and processes both in situ in the adult brain and in primary cultures. Overall, our results demonstrate specific subcellular localizations of CRMP1, CRMP2A, CRMP2B, and CRMP5 depending on cell types, neuronal compartment, and developmental stage. This study suggests that, beyond their signalling function in axon outgrowth and guidance, CRMPs also play a role in mature neurons both in axons and in dendrites.

    The Journal of comparative neurology 2005;486;1;1-17

  • Expression of collapsin response mediator proteins 1, 2 and 5 is differentially regulated in newly generated and mature neurons of the adult olfactory system.

    Veyrac A, Giannetti N, Charrier E, Reymond-Marron I, Aguera M, Rogemond V, Honnorat J and Jourdan F

    UMR 5020, Neurosciences et systèmes sensoriels, CNRS-Université Claude Bernard Lyon 1, 50 Avenue Tony Garnier, F-69366 Lyon cedex 07, France.

    Collapsin-response mediator proteins (CRMPs) are highly expressed in the developing brain where they take part in several aspects of neuronal differentiation. CRMPs are still present postnatally, but their function remains speculative in the adult brain. We studied the expression and localization of CRMP1, CRMP2 and CRMP5 in two areas of the nervous system with persistent neurogenesis in adult mice, the olfactory mucosa and the olfactory bulb. In the olfactory mucosa, we have established that CRMP expression is restricted to postmitotic cells of the olfactory neurons lineage. CRMP5 is coexpressed with growth associated protein of 43 kDa (GAP43) in immature olfactory neurons and is down-regulated in olfactory marker protein-positive mature neurons. In contrast, CRMP1 and CRMP2 persist at all stages of differentiation from immature GAP43-positive to fully mature olfactory neurons. In the olfactory bulb, CRMP1, CRMP2 and CRMP5 are abundant in neuronal progenitors of the subependymal layer and in differentiating interneurons. In both areas, the subcellular distribution of CRMP1 or CRMP2 is different in mature vs. immature neurons, suggesting that these proteins are sequentially involved in various cellular events during neuronal lifetime. The variations of CRMP expression following axotomy are consistent with their differential localization and functional involvement in immature vs. mature neurons of the olfactory system. Our data bring new insight to the putative functions of CRMPs within areas of the adult nervous system with permanent neurogenesis, some related to differentiation of newly generated neurons but others occurring in mature neurons with a limited lifespan.

    The European journal of neuroscience 2005;21;10;2635-48

  • Critical role of collapsin response mediator protein-associated molecule CRAM for filopodia and growth cone development in neurons.

    Hotta A, Inatome R, Yuasa-Kawada J, Qin Q, Yamamura H and Yanagi S

    Division of Proteomics, Department of Genome Sciences, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.

    Collapsin response mediator proteins (CRMPs) have been implicated in signaling of axonal guidance, including semaphorins. We have previously identified a unique member of this gene family, CRMP-associated molecule CRAM (CRMP-5), which is phylogenetically divergent from the other four CRMPs. In this study, we have examined the distribution and function of CRAM in developing neurons. Immunohistochemical analysis showed accumulation of CRAM in the filopodia of growth cones. Experiments using cytochalasin D indicated that filopodial localization of CRAM was independent of filamentous actin. Overexpression of CRAM in neuronal cells significantly promoted filopodial growth and led to the formation of supernumerary growth cones, which acquired resistance to semaphorin-3A stimulation. Finally, knockdown of CRAM by using RNA interference blocked filopodial formation and revealed an aberrant morphology of growth cones. We propose that CRAM regulates filopodial dynamics and growth cone development, thereby restricting the response of growth cone to repulsive guidance cues.

    Molecular biology of the cell 2005;16;1;32-9

  • 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

  • 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

  • Molecular characterization of CRMP5, a novel member of the collapsin response mediator protein family.

    Fukada M, Watakabe I, Yuasa-Kawada J, Kawachi H, Kuroiwa A, Matsuda Y and Noda M

    Division of Molecular Neurobiology, National Institute for Basic Biology, and Department of Molecular Biomechanics, Graduate University for Advanced Studies, Okazaki 444-8585, Japan.

    The CRMP (collapsin response mediator protein) family is thought to play key roles in growth cone guidance during neural development. The four members (CRMP1-4) identified to date have been demonstrated to form hetero-multimeric structures through mutual associations. In this study, we cloned a novel member of this family, which we call CRMP5, by the yeast two-hybrid method. This protein shares relatively low amino acid identity with the other CRMP members (49-50%) and also with dihydropyrimidinase (51%), whereas CRMP1-4 exhibit higher identity with each other (68-75%), suggesting that CRMP5 might be categorized into a third subfamily. The mouse CRMP5 gene was located at chromosome 5 B1. Northern blot and in situ hybridization analyses indicated that CRMP5 is expressed throughout the nervous system similarly to the other members (especially CRMP1 and CRMP4) with the expression peak in the first postnatal week. Association experiments using the yeast two-hybrid method and co-immunoprecipitation showed that CRMP5 interacts with dihydropyrimidinase and all the CRMPs including itself, except for CRMP1, although the expression profile almost overlaps with that of CRMP1 during development. These results suggest that CRMP complexes in the developing nervous system are classifiable into two populations that contain either CRMP1 or CRMP5. This indicates that different complexes may have distinct functions in shaping the neural networks.

    The Journal of biological chemistry 2000;275;48;37957-65

  • Conditional gene expression in the epidermis of transgenic mice using the tetracycline-regulated transactivators tTA and rTA linked to the keratin 5 promoter.

    Diamond I, Owolabi T, Marco M, Lam C and Glick A

    Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, Maryland, USA.

    To produce conditional expression of genes in the mouse epidermis we have generated transgenic mouse lines in which the tetracycline-regulated transcriptional transactivators, tTA and rTA, are linked to the bovine keratin 5 promoter. The transactivator lines were crossed with the tetOlacZ indicator line to test for transactivation in vivo. In the absence of doxycycline, the K5/tTA line induced beta-galactosidase enzyme activity in the epidermis at a level 500-fold higher than controls, and oral and topical doxycycline caused a dose- and time-dependent suppression of beta-galactosidase mRNA levels and enzyme activity. In the K5/rTA lines, doxycycline induced beta-galactosidase activity between 3- and 50-fold higher depending on the founder line, and this occurred within 24-48 h after dosing. Histochemical analysis of all lines localized beta-galactosidase expression to the basal layer of the epidermis and the outer root sheath of the hair follicle, as well as other keratin 5 positive tissues. In several K5/rTA lines, skin-specific transactivation was restricted to the hair follicle. Treatment of these double transgenic mice with 12-O-tetradecanoyl-phorbol-13-acetate caused rapid migration of beta-galactosidase marked cells from the hair follicle through the interfollicular epidermis, demonstrating the usefulness of this specific double transgenic for fate mapping cells in the epidermis. These results show that the tetracycline regulatory system produces effective conditional gene expression in the mouse epidermis, and suggest that it should be amenable to suppression and activation of foreign genes during development and specific pathologic conditions relevant to the epidermis.

    The Journal of investigative dermatology 2000;115;5;788-94

Gene lists (4)

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
L00000008 G2C Mus musculus Mouse PSP Mouse PSP adapted from Collins et al (2006) 1121
© 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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