Methods comprising apoptosis inhibitors for the generation of transgenic pigs

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Stem Cell Related Patent Number US5955644

Title:Ku deficient cells and non-human transgenic animals
Inventors:Hasty, Paul; Magnolia, TX, USA
Summary:This invention describes cells and transgenic animals containing a XRCC5 mutation, and which are deficient in Ku. Ku deficient cells and transgenic animals are described that comprise at least one allele of the XRCC5 gene that has been mutated by targeted disruption. Fibroblasts derived from XRCC5 mutant embryos and mice were found to age prematurely, thereby displaying decreased growth, slow entry into S phase, altered colony size distribution that favored small colonies, short life span and morphology characteristic of terminal differentiation. Mutant cells were also hypersensitive to gamma -radiation. The tissue culture data was at least partly reproduced in vivo because mutant mice grew slower than control littermates. The XRCC5 mutation, designated xrcc5M1, was a deletion of nucleotides 701-964 that shifted the reading frame. It is thus expected that xrcc5M1 will be null because the deleted allele produced no detectable transcript and also because lymphocyte development and V(D)J recombination was severely disrupted. Further provided are potential therapeutic uses in disease models for analysis and testing of agents and the effects of mutagens.
Abstract:Ku deficient cells and transgenic animals are described that comprise at least one allele of the XRCC5 gene that has been mutated by targeted disruption. Fibroblasts derived from XRCC5 mutant embryos and mice were found to prematurely age. These cells displayed decreased growth, slow entry into S phase, altered colony size distribution that favored small colonies, short life span and morphology characteristic of terminal differentiation. Mutant cells were also hypersensitive to .gamma.-radiation. The tissue culture data was at least partly reproduced in vivo because mutant mice grew slower than control littermates. The XRCC5 mutation, designated xrcc5.sup.M1, was a deletion of nucleotides 701-964 that shifted the reading frame. xrcc5.sup.M1 is expected to be null because the deleted allele produced no detectable transcript and because lymphocyte development and V(D)J recombination was severely disrupted.
US Patent Website:Click Here for Full Text of Patent
Title Number:US5955644
Application Number:US1996000695866
Date Filed:08/08/1996
Date Published:21/09/1999
Assignee:M.D. Anderson Cancer Center, Houston, TX, USA


 
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