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  • The 16th International Mouse Genome Conference (2002)
    ZEBRAFISH NEUROGENIC MUTATION R Rajendra Molecular Genetics and Microbiology Wu J Artzt K University of Texas at Austin We are analyzing a gene that was identified originally in zebrafish in a retroviral insertional mutant screen done in the Hopkins lab M I T Cancer Center This mutant Hi904 is an allele of the zebrafish mutant mind bomb mib It is a homozygous recessive lethal on day 5 of development and has a phenotype that is detectable at 33 hours post fertilization Progressive temporal disorganization of the neural epithelium is observed Histological analysis reveals that the neuro epithelium develops normally initially but later loses its architecture and rounded cells start to fill the brain cavity This pattern appears to be typical of a neural tumor that occurs in young children Homology searches have revealed that this gene is highly conserved from Drosophila onwards The mouse gene referred to as mib1 maps to chromosome 18 at 3 0 cM mib1 spans almost 91 Kb coding for a 10 Kb transcript which translates into an 110 kDa protein A mouse knockout of mib1 is being generated The expression pattern of mib1 that is being characterized using in situ hybridization has been found mainly

    Original URL path: http://www.imgs.org/Archive/abstracts/2002abstracts/file35.shtml (2016-02-17)
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  • The 16th International Mouse Genome Conference (2002)
    AND BIOCHEMICAL ANALYSIS OF A NEW PUTATIVE E3 LIGASE G Gao ICMB Wu J Artzt K ICMB University of Texas at Austin U S A A mutant first identified in zebrafish mind bomb 1 mib1 is currently being analyzed with reference to another vertebrate the mouse This gene encodes a novel protein of 1000 amino acids The protein sequence indicates a putative E3 ligase with three RING fingers Other domains include a ZZ type Zinc finger flanked by two novel WXW domains and eight ankyrin repeats By searching ESTs in the database a second homologue mib2 has been identified Both mib1 and mib2 are conserved in Drosophila zebrafish and mammals The mouse mib2 is 54 similar to mouse mib1 and 89 homologous to human mib2 In zebrafish mib1 is a recessive lethal with a known serious disorder of the entire neuroepithelium tissue Thus it would be interesting to determine the functions of mib2 and characterize any phenotype in the mouse mib2 is located on mouse chromosome 4 at 79 4 cM and in human at 1p36 33 The Mib2 protein is ubiquitously expressed in mouse Using RT PCR two alternative splice isoforms of mib2 have been cloned The first mib2

    Original URL path: http://www.imgs.org/Archive/abstracts/2002abstracts/file36.shtml (2016-02-17)
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  • The 16th International Mouse Genome Conference (2002)
    College of Medicine Retinoic acid RA plays an integral role in vertebrate development Synthesis of RA during early development is regulated via retinaldehyde dehydrogenase 2 Raldh2 dependent conversion of dietary retinal to RA We examined mice deficient for Raldh2 to determine whether vascular and hematopoietic defects are associated with RA deficiency We determined that in Raldh2 mice endothelial cell differentiation and tube formation occurred but the initial capillary plexus that formed failed to remodel and recruit mural cells smooth muscle cells and pericytes to form a surrounding vessel wall Immunostaining further revealed a 1 5 2 fold increase in endothelial cell proliferation in 8 5dpc Raldh2 yolk sacs compared to wildtype and a significant decrease in the expression of cell cycle inhibitors p21 and p27 Semi quantitative RT PCR analysis of RNA isolated from 8 5dpc Raldh2 yolk sacs revealed down regulation of multiple signaling pathways known to be involved in blood vessel assembly as well as decreased expression of RNA binding protein quaking compared to wildtype littermates Administration of RA to the pregnant mother from 7 5 8 5dpc 7 5 9 5dpc or 7 5 12 5dpc progressively decreased endothelial cell proliferation upregulated key signaling molecules including quaking

    Original URL path: http://www.imgs.org/Archive/abstracts/2002abstracts/file37.shtml (2016-02-17)
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  • The 16th International Mouse Genome Conference (2002)
    STEM CELLS M Carter Developmental Genomics Aging Section Laboratory of Genetics National Institute on Aging NIH 1 Hamatani T 1 Sharov A 2 Carmack C 1 Qian Y 2 Brzoska P 2 Hwang S 1 Ko M 1 NIA 2 Agilent Inkjet based in situ 60 mer oligo synthesis technology allows more rapid and flexible microarray design without labor intensive clone handling required by cDNA array production However for downstream experimental work on genes implicated by microarray experiments a collection of readily available cDNA clones corresponding to these oligos is essential To this end we have designed and constructed an in situ synthesized microarray representing approximately 21 000 unique genes at least 98 of which correspond to clones in the unique cDNA collections of NIA As an initial performance assessment we have generated oligo array expression profiles of mouse E12 5 embryo and placenta and compared them to similar profiles previously published using the NIA 15K cDNA microarray platform For over 11 000 unique genes represented on both platforms we compared the expression ratios obtained and their statistical significance The oligo array measured more significant expression changes than the cDNA array especially at low expression ratios and many genes which

    Original URL path: http://www.imgs.org/Archive/abstracts/2002abstracts/file38.shtml (2016-02-17)
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  • The 16th International Mouse Genome Conference (2002)
    2 Carpenter D 2 Rinchik E 2 Culiat C 1 Genome Science and Technology Graduate School The University of Tennessee 2 Life sciences Division Oak Ridge National Laboratory A locus l7R6 critical for late embryonic development and survival has been mapped proximal to the pink eyed dilution p gene in mouse chromosome 7 Eight independent ENU induced alleles designated 88SJ 335SJ 2038SJ 102DSJ 11DSJ 45DSJ 141DSJ and 244DSJ have been recovered for l7R6 and all result in late gestation lethality Complementation analysis of l7R6 mutations with p deletions maps the gene s to a region homologous to human 11p15 1 where a very large gene for a novel protein kinase C binding protein called NELL1 is located Because the human gene is so large and we recovered so many l7R6 alleles in a relatively small number of gametes screened the mouse Nell1 gene was evaluated as a candidate for l7R6 Northern Blot analysis showed that Nell1 was normally expressed throughout fetal development and increases dramatically in the head at late gestation In adult mice expression was detected predominantly in brain A severely reduced level of Nell1 expression was observed in the 102DSJ allele Abnormal expression of human NELL1 is associated

    Original URL path: http://www.imgs.org/Archive/abstracts/2002abstracts/file39.shtml (2016-02-17)
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  • The 16th International Mouse Genome Conference (2002)
    Millar S 5 Stubbs L 3 Siedman C 3 Olson E 1 Beier DR 1 Brigham and Womans Hospital 2 UT Southwestern 3 Harvard Medical School 4 University of Pennsylvania 5 Joint Genome Institute We have identified a novel recessive mutation in mice that causes abnormalities of the heart and skin We have named this mutation waved 3 because affected mice have open eyelids at birth and a curled coat

    Original URL path: http://www.imgs.org/Archive/abstracts/2002abstracts/file40.shtml (2016-02-17)
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  • The 16th International Mouse Genome Conference (2002)
    LL Justice MJ Hirschi KK Baylor College of Medicine We recently determined that a mutation in the RNA binding domain of quaking yields lethal defects in vascular development Analysis of the expression of PE CAM 1 Tie 2 and SM a actin proteins revealed that embryos homozygous for the qkk2 allele exhibit normal endothelial cell commitment and differentiation but lack endothelial cell maturation and mural cell recruitment resulting in abnormal vascular remodeling Importantly these mutants exhibit normal cardiac muscle differentiation and cardiac function at this stage of embryonic development Thus these results suggest that quaking plays a primary role in vascular development We aimed to elucidate the underlying cellular and molecular role s of quaking in blood vessel formation and investigate whether quaking regulates hematopoietic development Our studies revealed down regulation of multiple signaling pathways known to be involved in blood vessel assembly including hedgehog VEGF and TGF b pathways as revealed by semi quantitative RT PCR of RNA isolated from yolk sacs of qkk2 mutants and wild type littermates Furthermore a decrease in the expression of Tal 1 suggests defects in blood cell commitment and or differentiation Interestingly the phenotype of the qkk2 mutants parallels that of embryos deficient

    Original URL path: http://www.imgs.org/Archive/abstracts/2002abstracts/file41.shtml (2016-02-17)
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  • The 16th International Mouse Genome Conference (2002)
    CLUSTER R Holmes MRC Harwell 2 Wells C 3 Monk D 1 Williamson C 1 Peters J 1 MRC Harwell 2 University of QLD 3 Imperial College The Gnas cluster on mouse distal Chr 2 produces a number of oppositely imprinted and alternatively spliced transcripts namely Nesp Gnasxl and exon 1A from the sense strand and Nespas from the antisense strand To determine the full extent of the cluster we have analysed the imprinting status of genes immediately flanking Gnas these comprise Rabb22a Vapb Stx16 and Npepl1 which are proximal to Gnas and Th1 Tubb1 and Edn3 which lie distal to Gnas All were biallelically expressed indicating that the imprinting domain on distal Chr 2 maybe as small as 65kb the size of the Gnas cluster To identify novel transcripts within the imprinted cluster we have analysed the imprinting status of FANTOM2 cDNAs and new ESTs Ten new imprinted transcripts have been detected Five new maternal transcripts have been identified between Nesp and Gnasxl and upstream of exon 1A and which probably represent alternatively spliced forms of Nesp Further investigations show that one of these is expressed tissue specifically in the pituitary in 17 5dpc embryos Of the five paternally

    Original URL path: http://www.imgs.org/Archive/abstracts/2002abstracts/file42.shtml (2016-02-17)
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