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  • The 16th International Mouse Genome Conference (2002)
    Shimizu K 3 Yada Y 4 Tamura M 5 Shiroishi T 1 RIKEN GSC 2 Nihon University 3 Ochanomizu University National Institute of Genetics 4 National Institute of Genetics 5 National Institute of Genetics RIKEN GSC Preaxial polydactyly is the most common limb abnormality in human and mouse A locus for the major form of the human preaxial polydactyly has been mapped to7q36 In the mouse syntenic region which is closely linked to shh on chromosome 5 several preaxial polydactyly mutations have been mapped Their phenotypes are characterized by mirror image digit duplication and ectopic expression of shh in the anterior limb margin The human LMBR1 and the mouse homologue Lmbr1 genes that reside at 1Mb apart from shh is one of the most possible candidates for these mutations In a human mutation Acheiropodia which exhibits limb truncation the LMBR1gene has a large deletion including exon4 By contrast in the mouse mutations no alteration was observed in the Lmbr1 gene Very recently it was reported that the alteration of a cis element of shh which resides in intron 5 of Lmbr1 may result in a preaxtial polydactyly mutation Ssq Lettice et al 2002 We have carried out positional cloning for

    Original URL path: http://www.imgs.org/Archive/abstracts/2002abstracts/file51.shtml (2016-02-17)
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  • The 16th International Mouse Genome Conference (2002)
    NHGRI The epidermis is a multilayered tissue with an inner basal layer of proliferating cells and suprabasal layers of progressively differentiating cells Located at the interface between body and environment one of its roles is to act as a barrier to protect against dehydratation In mice the epidermal barrier function starts to establish around embryonic day E16 5 and is fully established at day E17 5 KLF4 is a zinc finger transcription factor of the Kruppel like family expressed in epithelial cells of different organs mainly skin lungs and gut Knock out mice for Klf4 gene showed that this transcription factor is required for establishing the skin barrier function To further characterize the exact role of KLF4 in this process we chose to study the effect of a gain of function of KLF4 We overexpressed KLF4 one stage earlier in development i e in the basal layer of the epidermis instead of the suprabasal layers using a conditional approach with the tetracycline system We used a previously established driver line bovin promoter of keratin 5 gene and constructed a myc tagged KLF4 responder line A dye penetration assay showed that double transgenic mice establish their barrier earlier than wild type

    Original URL path: http://www.imgs.org/Archive/abstracts/2002abstracts/file52.shtml (2016-02-17)
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  • The 16th International Mouse Genome Conference (2002)
    Tamura M 5 Shiroishi T 1 Grad Univ Advanced Studies Natl Inst Genet 2 Natl Inst Genet Juntendo Univ 3 Tohoku Univ 4 Natl Cancer Cent Res Inst 5 Grad Univ Advanced Studies Natl Inst Genet Epidermis and hair follicles are generated from epidermal stem cells that have an ability of self renewal The epidermal stem cells reside in both basal layer and bulge of hair follicles While the stem cells in basal layer differentiate into epidermal keratinocytes those in bulge give rise not only to hair follicles but also to epidermis However the molecular mechanism by which epidermal stem cells differentiate is poorly understood Recombination induced mutation 3 Rim3 is a mouse mutation that exhibits hyperkeratosis and hair follicle degeneration To characterize the epidermis of Rim3 we analyzed proliferation of the epidermal cells by BrdU labeling and carried out immunohistochemical analysis with epidermal cells specific marker We found hyperproliferation of the upper follicular epidermis and it appeared that cells in the hair follicles differentiate into epidermal keratinocytes These data suggest that the bulge stem cells differentiate epidermal keratinocytes and the progeny cell migrates upward to the follicular epidermis rather than to the lower hair follicles which results in hair

    Original URL path: http://www.imgs.org/Archive/abstracts/2002abstracts/file53.shtml (2016-02-17)
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  • The 16th International Mouse Genome Conference (2002)
    Clore J Threadgill DW University of North Carolina Chapel Hill Department of Genetics The epidermal growth factor receptor Egfr is a 170 kilodalton protein containing a ligand binding single transmembrane and cytoplasmic tyrosine kinase domain Upon ligand binding Egfr activates intracellular signaling cascades to effect cell growth and or differentiation The Egfr is normally expressed in a number of adult tissues and misexpressed in a variety of human cancers of epithelial origin Mice homozygous for a null allele of Egfr Egfrtm1Mag display variable phenotypes depending on genetic background A reduction in the number of spongiotrophoblast cells has been observed in placentae of Egfr null homozygotes on all genetic backgrounds tested In order to determine the molecular mechanism behind the placental defects the levels of proliferation were quantified in both Egfr null and wild type placentae at e10 5 e13 5 and e18 5 At e10 5 BrdU incorporation was reduced in the Egfr null placenta relative to wild type however PCNA staining was increased in the Egfr null placenta Since BrdU specifically labels cells actively undergoing S phase of the cell cycle and PCNA is detected during S G2 and M phases we hypothesize that the Egfr null placenta has

    Original URL path: http://www.imgs.org/Archive/abstracts/2002abstracts/file54.shtml (2016-02-17)
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  • The 16th International Mouse Genome Conference (2002)
    of Genetics 1 Yada Y 2 Masuya H 3 Makino S 4 Shiroishi T 1 Ochanomizu University National Institute of Genetics 2 RIKEN GSC 3 National Institute of Genetics 4 National Institute of Genetics RIKEN GSC Recombination induced mutation 4 Rim4 is a spontaneous mouse mutation that arose in intra MHC recombinants at National Institute of Genetics Mishima Japan Rim4 heterozygotes have an extra triphalangeal digit on the preaxial side of the digit 1 of the hindlimbs while homozygotes have two or three extra triphalangeal digits instead of the digit 1 in the fore and hindlimbs In addition Rim4 homozygotes exhibit tibial hemimelia and sacralization of the presacral vertebrae To study the molecular basis underlying Rim4 phenotype we analyzed the expression patterns of several marker genes in the limb buds of Rim4 embryos It is known that ectopic expression of Shh and Fgf4 are observed at the anterior margin of the Rim4 limb buds Their expression however is detected in the later stage after the aberration of the limb shape becomes apparent Therefore we examined the expression of marker genes in the early stage limb buds We found that in Rim4 limb buds the expression domains of Shh Fgf4 and

    Original URL path: http://www.imgs.org/Archive/abstracts/2002abstracts/file55.shtml (2016-02-17)
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  • The 16th International Mouse Genome Conference (2002)
    Sachot S Orhant M Gicquel I Mottier S Soriano N Mosser J UMR 6061 CNRS Faculté de Médecine We aimed to precise the regulatory mechanisms involved in intestinal iron absorption which dysfunction leads to anemia or iron overload For this purpose we used transgenic models of targeted expression of HFE in gut epithelium HFE Bahram et al 1999 and HFE knock out bred with HFE transgenic mice Fergelot et al 2002 These mice provide integrative models to study the role of HFE1 the gene mutated in hereditary hemochromatosis on iron transfer during enterocyte differentiation We are now developing a transcriptomic approach to correlate the pattern of expression of cryptic and mature enterocytes with their HFE status Transcriptomic analysis was initiated on intestinal cell lines to select a subset of genes that could be differentially expressed in varied biological conditions cDNAs clones obtained after subtractive suppressive hybridization SSH between undifferentiated and differentiated Caco2 intestinal cell line were spotted and hybridized with mouse mRNA from cryptic cells or differentiated enterocytes Due to a considerable variation of differentially expressed clones with strigency conditions we built cDNA microarrays dedicated to murine tissues SSH between the whole duodenal cells of HFE mice and transgenic mice

    Original URL path: http://www.imgs.org/Archive/abstracts/2002abstracts/file56.shtml (2016-02-17)
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  • The 16th International Mouse Genome Conference (2002)
    Bouck J 1 Tang P 1 McEuen M 1 Paeper B 1 Britschgi T 1 Bennington A 1 Proll S 1 Bobick S 1 Tittel P 1 Wasnick M 1 Snell A 1 Palmberg G 2 Carlson G 1 Schatzman R 1 Celltech R D Inc 2 McLaughlin Research Institute The Celltech ENU Mutagenesis program is focused primarily on identifying novel clinically relevant targets in the areas of inflammation autoimmunity and lymphocyte biology We have implemented a number of in vitro and in vivo screens designed to identify mutations specifically affecting the function of the immune system including activation of T and B cells T dependent and T independent inflammatory responses and mouse models of colitis and graft versus host disease Screening exclusively for recessive phenotypes we have identified nearly 100 phenodeviants which have entered into the mapping process We have developed an integrated laboratory informatic pipeline which enables rapid identification of a candidate interval and the genes contained within as well as efficient tracking of gene testing results capturing both exon sequencing and gene expression data Our development and utilization of informatics tools has proven critical in the effective management of the program We maintain an ongoing process of

    Original URL path: http://www.imgs.org/Archive/abstracts/2002abstracts/file57.shtml (2016-02-17)
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  • The 16th International Mouse Genome Conference (2002)
    ANALYSIS OF MOUSE MUTANTS J Beckers GSF National Research Center for Environment Health Drobyshev A Machka C Horsch M Hrabe de Angelis M Beckers J GSF National Research Centre for Environment Health The cDNA chip technology is a powerful tool for the comprehensive analysis of gene expression at the transcript level The biological significance of such expression profiling analyses critically depends on the quality and specificity of hybridisation data Based on experimental data we describe methods to discriminate between gene specific signals and signals resulting from extensive cross hybridisation We identify criteria that can be used for each individual probe on comprehensive DNA chips to correct expression data to achieve high quality results For this we apply in situ fractionation of hybridised targets by means of contiguous washes with increasing stringency In the course of such washing steps distinct fractions of hybridised target are washed out at different stringency The fluorescent intensity data at each step and for each probe of a microarray comprise the fractionation curve Based on this information unreliable data can be filtered and gene specific probes relevant for high quality expression data can be identified In the MouseExpress project we apply this technology for a systematic

    Original URL path: http://www.imgs.org/Archive/abstracts/2002abstracts/file58.shtml (2016-02-17)
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