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  • 18th International Mouse Genome Conference (2004)
    1 1 GNF San Diego United States 2 Celera Genomics Rockville United States 3 The Jackson Laboratory Bar Harbor United States Single nucleotide polymorphisms SNPs that occur between mouse strains may produce a specific functional change in a gene leading to phenotypic variation but are more often simply markers for an ancestral haplotype In silico mapping provides an expedient way to associate the natural diversity of phenotypic traits with ancestrally inherited polymorphisms for the purposes of dissecting genetic traits The goal of in silico mapping is to identify which haplotype patterns track with a specific phenotype with the idea that the tracking haplotype contains a causative mutation For in silico mapping to be successful a dense SNP map is required and multi strain phenotypes data well defined In mouse the current SNP data has lacked the density across the genome and coverage of enough strains to properly achieve this goal To remedy this 467 015 allele calls were produced for 10 917 evenly spaced SNP loci across 48 inbred mouse strains Phenotype data for multiple strains is now available through the Phenome project Use of the SNP set with statistical models that considered unique patterns within blocks of 3 SNPs

    Original URL path: http://www.imgs.org/Archive/abstracts/2004abstracts/abs/file17.shtml (2016-02-17)
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  • 18th International Mouse Genome Conference (2004)
    potential for the treatment of viral infections Our laboratory has focused on liver directed transfer of siRNAs and the expression of short hairpin RNAs from the livers of living animals to inhibit transgene expression To do this we injected either the short inhibitory RNAs or plasmids expressing the short hairpins along with a plasmid expressing the luciferase transgene luciferase HCV fusion gene or HBV genome into the livers of mice by a hydrodynamic infusion procedure We established that 1 RNAi was functional in whole mammals 2 Expressed shRNAs were efficient at down regulating gene expression suggesting that RNAi mediated therapies can be adapted to a gene therapy approach 3 RNAi against hepatitis C virus sequences were inhibitory and 4 shRNAs directed against hepatitis B virus inhibited viral HBV DNA replication in the liver To further pursue a gene therapy approach against hepatitis virus infection in animal models a transgenic mouse that contains and replicates the HBV genome was used for further study shRNAs expressed from pol III promoters were cloned into first generation or helper dependent adenoviral gene deleted adenovirus and AAV pseudotype 8 recombinant viral vectors and then infused into the HBV transgenic mice These three vector systems were

    Original URL path: http://www.imgs.org/Archive/abstracts/2004abstracts/abs/file3.shtml (2016-02-17)
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  • 18th International Mouse Genome Conference (2004)
    TRANSPOSON SYSTEM Takeda J 1 Keng VW 1 Yae K 1 Hayakawa T 1 Mizuno S 1 Uno Y 2 Kokubu C 1 Horie K 1 1 Dept of Social and Environmental Medicine Osaka University Graduate School of Medicine Osaka Japan 2 The Institute of Experimental Animal Science Osaka University Osaka Japan Generation of mutant mice is important in determining the function of genes in the post genome era Sleeping Beauty SB is a synthetic transposon derived from a fish genome and we have previously demonstrated that the SB transposon sytem worked efficiently in mouse germ line suggesting a potential usage of a large scale mutagenesis in mice We also observed that about 80 of transposition events in germ cell preferentially occurred near the donor site and within the same chromosome After screening about 600 mice the number of transposon integrated gene hits was shown to be clustered within approximately 3 Mb distance of the donor site From a double positive containing SB transposase and transposon acting as a mutagen transgenic mouse with donor site located on chromosome 12 we obtained 16 clustered transposon integrations corresponding to about 50 of known genes located within the 3 Mb region This indicates

    Original URL path: http://www.imgs.org/Archive/abstracts/2004abstracts/abs/file18.shtml (2016-02-17)
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  • 18th International Mouse Genome Conference (2004)
    J Sedlmeier R Peters T Huffstadt U Wattler S Nehls M Ingenium Pharmaceuticals Martinsried Germany Mouse and rats are the model of choice for in vivo studies of gene function but the development of knockouts and allelic variants i e hypo and hypermorphs is time consuming and costly The generation of mouse models is dominated by gene targeting through homologous recombination which requires sophisticated ES cell manipulation and chimera production No such standard procedure for the development of targeted rat models is available despite some first success in nuclear cloning of rats from unmodified somatic cells In order to make rat and mouse models with genetic alterations readily available to the scientific community we developed a patented technology named INGENOtyping TM based on gene saturating chemical mutagenesis We first applied INGENOtyping TM to generate a pre set library of mutagenized murine sperm that represents multiple alterations in every mouse gene Currently somatic DNA and corresponding sperm samples of more than 15 000 mice derived from a well controlled chemical mutagenesis process using ENU have been archived and can be screened for mutations in any gene of interest within days Together with the subsequent extremely efficient in vitro fertilization the adult

    Original URL path: http://www.imgs.org/Archive/abstracts/2004abstracts/abs/file19.shtml (2016-02-17)
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  • 18th International Mouse Genome Conference (2004)
    1 Hart AW 1 Morgan JE 1 McKie L 1 West K 1 Schneider JE 2 Bhattacharya S 2 Jackson IJ 1 1 MRC Human Genetics Unit Edinburgh United Kingdom 2 Wellcome Trust Centre for Human Genetics Oxford United Kingdom ENU mutagenesis is a powerful tool for revealing gene function We have produced a collection of 25 ENU induced mutants with a variety of eye defects and most of these are homozygous lethal Three Rwhs Icst and Dilp2 an X linked male lethal map to novel loci We used high throughput magnetic resonance imaging MRI of embryos to determine the mechanism of lethality in these mutants This enables us to screen 32 embryos per overnight run retains 3D information and allows embryos to be examined in any section plane Using MRI we found that Rwhs homozygotes have pulmonary hypoplasia and Bochdalek congenital diaphragmatic hernia This malformation is present in 1 2500 live births and even with corrective surgery has a mortality of 30 Icst homozygotes have a ventricular septal defect and aberrant right sided aortic arches Dilp2 males have a common arterial trunk a condition that accounts for 1 of all congenital heart defects In addition they have palate defects

    Original URL path: http://www.imgs.org/Archive/abstracts/2004abstracts/abs/file20.shtml (2016-02-17)
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  • 18th International Mouse Genome Conference (2004)
    Hdlq5 a major QTL for plasma high density lipoprotein cholesterol HDL levels on mouse chromosome 1 First we performed a sequence analysis of the Apoa2 coding region in 46 genetically diverse mouse strains and found five different APOA2 protein variants which we named APOA2 a to APOA2 e Second we conducted a haplotype analysis of strains in 21 crosses that have so far detected HDL QTLs and found that Hdlq5

    Original URL path: http://www.imgs.org/Archive/abstracts/2004abstracts/abs/file21.shtml (2016-02-17)
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  • 18th International Mouse Genome Conference (2004)
    and cytokines induced transcription of the Mt1 gene The Mt locus is amplified in cells resistant to cadmium toxicity but inactivated by DNA methylation in other cell lines In pursuit of understanding the transcriptional regulation by metals we fused the 5 flanking region of Mt1 gene to the coding region of HSV thymidine kinase to produce MT TK and sent it to Ralph Brinster for injection into mouse eggs These experiments along with mutational analysis were used to identify the metal response elements that allow induction by metals More importantly they launched a 15 year collaboration with Ralph Brinster making and studying genetically modified mice The MT TK transgenic mice were the first that demonstrated expression regulation methylation and germline transmission of a functional transgene Input from Vern Chapman and colleagues at Roswell Park in 1981 contributed to the big mouse experiments that demonstrated how transgenic technology could alter the phenotype of mice While endeavouring to understand how enhancers work we discover that SV40 T antigen is a potent oncogene Meanwhile the odd transmission of MT TK transgene in one line of mice in which males were fertile but never transmitted the transgene let to the discovery of HSV TK

    Original URL path: http://www.imgs.org/Archive/abstracts/2004abstracts/abs/file4.shtml (2016-02-17)
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  • 18th International Mouse Genome Conference (2004)
    that enable genomic DNA cloned into plasmids PACs or BACs to be modified or subcloned directly in E coli without the need for restriction enzymes or DNA ligases This new form of chromosome engineering termed recombineering is highly efficient and greatly decreases the time it takes to create transgenic or knockout mouse models by conventional means Recombineering also facilitates many kinds of genomic experiments that have been difficult if not

    Original URL path: http://www.imgs.org/Archive/abstracts/2004abstracts/abs/file5.shtml (2016-02-17)
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