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  • 17th International Mouse Genome Conference (2003)
    1 Lengeling A Institutions 1 Junior Research Group Infection Genetics German Research Centre for Biotechnology GBF Mascheroder Weg 1 38124 Braunschweig 2 Institute of Medical Microbiology Immunology and Hygiene Technical University of Munich Trogerstr 4a 81675 München 3 Department of Experimental Immunology German Research Centre for Biotechnology GBF Mascheroder Weg 1 38124 Braunschweig 4 Institute of Experimental Genetics GSF Research Center of Environment and Health Ingolstaedter Landstrasse 1 85764 Neuherberg At the GBF in Braunschweig a mouse infection challenge platform has been established where mouse mutants with abnormalities in immune function can be tested for host defence against different pathogens This screen works in close collaboration with the German Mouse Clinic in Neuherberg where a comprehensive first line phenotyping of mouse mutants from various sources takes place Within the last two years we established detailed standardised protocols that allow us to monitor systematically host responses of mice after infection with Listeria monocytogenes Streptococcus pyogenes and Yersinia enterocoilitica This includes health status monitoring during infection analysis of survival bacterial dissemination and growth kinetics of pathogens in different organs In addition cytokine responses and the composition of immune effector cells in the peripheral blood are analysed Phenotyping and establishment of base line

    Original URL path: http://www.imgs.org/Archive/abstracts/2003abstracts/file259.shtml (2016-02-17)
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  • 17th International Mouse Genome Conference (2003)
    The Genetics and Genomics of Infectious Disease Verne Chapman Memorial Lecture Table of Contents Sponsor Exhibitor List Awards Photographs POSTER 212 INNATE IMMUNE RESPONSES IN THE WILD DERIVED MICE Poltorak A The Scripps Research Institute Co Authors Smirnova I Hoebe K Institutions The Scripps Research Institute Spontaneous mutations in classical laboratory inbred strains of mice have been extremely helpful for the analysis of immunologically relevant traits However their genetic polymorphism is rather limited In order to increase the number of polymorphisms of natural origin different species of Mus derived from wild progenitors can be used in studies of immune functions In order to identify new genes that may be involved in innate immune response we compared several inbred and wild derived strains of mice in their response to various agonists of toll like receptors Tlr family members In MOLF Ei MSM Ms and Spretus Ei strains we have observed a significant variability in responses to CpG Poly I C as well as to LPS MOLF Ei and MSM Ei mice are hypo responsive to poly I C In addition MOLF Ei strain has extremely low response to CpG TNF synthesis in Spretus Ei mice in response to LPS is significantly

    Original URL path: http://www.imgs.org/Archive/abstracts/2003abstracts/file260.shtml (2016-02-17)
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  • 17th International Mouse Genome Conference (2003)
    ENU MUTAGENESIS SCREENING IN THE MOUSE Rutschmann S The Scripps Research Institute La Jolla Co Authors Du X Beutler B Institutions The Scripps Research Institute La Jolla Infectious diseases are a leading cause of morbidity and mortality worldwide It is known that genetic variation foretells susceptibility to many of these diseases in both humans and animals Thus the positional identification of genes that are critical for host defense against infections looms as one of the greatest challenges in immunology The intracellular bacterium Listeria monocytogenes is one of the most studied model for such infections Resistance to this pathogen relies on both innate and adaptive immunity but many aspects of our defenses are still not completely understood To gain deeper insight into the nature of these immune responses infectious agents need to be considered in the context of their complex mammalian host For this reason an in vivo forward genetic approach has been undertaken We have therefore implemented a screen for germline mutant mice with enhanced susceptibility to Listeria infection 6 to 8 week old mice are inoculated intravenously with a standardized dose of Listeria a quantity non lethal for wild type mice but lethal for mutant animals Mice are then

    Original URL path: http://www.imgs.org/Archive/abstracts/2003abstracts/file261.shtml (2016-02-17)
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  • 17th International Mouse Genome Conference (2003)
    LOCUS CONFERS UNRESPONSIVENESS TO UNMETHYLATED DINUCLEOTIDE Tabeta K The Scripps Research Institute Co Authors Du X Hoebe K Goode J Mudd S Sovath S Beutler B Institutions The Scripps Research Institute In an effort to identify new innate immune phenotypes we have pursued a program of germline saturation mutagenesis with N ethyl N nitrosourea ENU in mice The germline mutants are produced on the C57BL 6 background and peritoneal macrophages from individual animals are screened for their competence to respond to various inducing agents A single strong phenodeviant was isolated as a non responder to oligodeoxynucleotides with unmethylated CpG dinucleotides motifs and called CpG1 The phenotype is transmissible in a dominant manner and fully penetrant on C57BL 6 background and was mapped to mouse chromosome 9 using a panel of microsatellite markers An isolated T C transition was detected in the TLR9 coding region of an affected animal which resulted in amino acid substitution of Pro for Leu at residue 499 of the polypeptide chain As TLR9 is the CpG receptor and is encoded by a gene within the chromosomal interval concerned we concluded that the mutation is responsible for the resistance to CpG stimulation found in CpG 1 CpG1

    Original URL path: http://www.imgs.org/Archive/abstracts/2003abstracts/file263.shtml (2016-02-17)
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  • 17th International Mouse Genome Conference (2003)
    9050 USA Co Authors 2 Kumánovics A 1 Yonekawa H 2 Fischer Lindahl K Institutions 1 The Tokyo Metropolitan Institute of Medical Science Tokyo 113 8613 Japan 2 Howard Hughes Medical Institute and Center for Immunology University of Texas Southwestern Medical Center Dallas Texas 75390 9050 USA The 4 megabase MHC in mammals is a mosaic Stretches of conserved genes separate regions of MHC class I or II genes that evolve rapidly by duplication and deletion The 350 kb H2 D Q region is such a stretch of mouse specific class I genes which has been characterized in some detail in 6 haplotypes b bc d k f and p Each contains a different number and selection of class I genes greatly complicating the naming of genes and definition of alleles H2 Q class I molecules can interact with CD8 T lymphocytes and NK cells of the immune system Cloning and mapping of the Q region from the p haplotype of strain B10 P hinted at the presence of new genes Q11 Q12 and Q13 rather than alleles of known genes Litaker et al 1996 Mammalian Genome 7 200 205 We therefore undertook to sequence this 200 kb region from

    Original URL path: http://www.imgs.org/Archive/abstracts/2003abstracts/file264.shtml (2016-02-17)
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  • The 16th International Mouse Genome Conference (2002)
    Models Human Disease and Pharmacogenetics Sequence Annotation and Comparative Analysis of Genomes Attendees Sponsors Table of Contents Photographs Awards PLENARY PRESENTATION SUNDAY 17 NOVEMBER 13 15 13 45 HRS Multi Species Sequence Exploration Targeted Studies of Vertebrate Genome Structure Function and Evolution E Green NIH Intramural Sequencing Center Co Authors The NISC Comparative Sequencing Program Institutions NISC Comparative Sequencing Program As a complement to ongoing efforts to sequence entire vertebrate genomes we are sequencing the same targeted genomic regions in multiple species To date 200 Mb of sequence from 12 non human species have been generated These data provide myriad opportunities for comparative sequence analyses For example sequences from each of the species are being examined for architectural features of interest in many cases revealing compositional and evolutionary characteristics for each vertebrate In addition the general patterns of sequence conservation are being assessed revealing important insights about the general extents of conservation among different species and among different genomic regions Finally these data constitute a unique resource for delineating and measuring the complete spectrum of mutational events that shape the mammalian genome In summary our data are yielding valuable reconnaissance information for guiding decisions about which genomes to sequence in

    Original URL path: http://www.imgs.org/Archive/abstracts/2002abstracts/file181.shtml (2016-02-17)
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  • The 16th International Mouse Genome Conference (2002)
    Jenkins National Cancer Institute Co Authors 1 Matesic L 1 Wilson S 1 O Sullivan T 2 Huang J 1 Yip R 1 Swing D 3 Russell L 1 Copeland N Institutions 1 National Cancer Institute 2 University of Hong Kong 3 Oak Ridge National Laboratory dilute d ashen ash and leaden ln are required for the polarized transport of melanosomes the specialized pigment containing organelles of melanocytes to the neighboring keratinocytes and eventually into coat hairs Recent positional cloning and biochemical studies have shown that d encodes unconventional myosin Va an actin based vesicle motor Myosin Va binds its cargo the melanosome by interacting with a receptor protein complex containing Rab27a encoded by ash and melanophilin encoded by ln a postulated Rab27a effector Rab27a binds to the melanosome first and then recruits melanophilin which in turn recruits myosin Va Binding of myosin Va to Rab27A and melanophilin is dependent on exon F an alternatively spliced exon in the myosin Va tail Interestingly the coat color defects observed in d ash and ln mice are suppressed by a loss of function mutation in a fourth gene dilute suppressor dsu dsu encodes a small protein with no known function or homology

    Original URL path: http://www.imgs.org/Archive/abstracts/2002abstracts/file184.shtml (2016-02-17)
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  • The 16th International Mouse Genome Conference (2002)
    genomes are now available in public databases awaiting functional annotation Gene trap mutagenesis provides three types of information not readily attainable by other random mutagenesis schemes mutant phenotype trapped sequence and reporter expression However the reliability efficiency and spectrum of current expression driven screens are restrained by the reliance on reporter gene expression in ES cells To circumvent this limitation we have designed a new expression driven screening platform by

    Original URL path: http://www.imgs.org/Archive/abstracts/2002abstracts/file185.shtml (2016-02-17)
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