Methods comprising apoptosis inhibitors for the generation of transgenic pigs

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Stem Cell Related Patent Number US6673986

Title:Generation of xenogeneic antibodies
Inventors:Kucherlapati, Raju; Darien, CT, USA
Jakobovits, Aya; Menlo Park, CA, USA
Klapholz, Sue; Stanford, CA, USA
Brenner, Daniel G.; Redwood City, CA, USA
Capon, Daniel J.; Hillsborough, CA, USA
Summary:Described herein are methods of modifying the genome of embryonic stem cells via yeast spheroplasts containing a yeast artificial chromosome comprised of a xenogeneic DNA segment. The invention relates to a transgenic mouse comprising in its germline a modified genome such that the modification comprises inactivated endogenous immunoglobulin heavy chain loci in which all of the J segment genes from both copies of the immunoglobulin heavy chain locus are deleted to prevent rearrangement and to prevent formation of a transcript of a rearranged locus and the expression of an endogenous immunoglobulin (Ig) heavy chain from the inactivated loci. The resultant non-human mammalian hosts are characterized by inactivated endogenous Ig loci and functional human Ig loci for response to an immunogen to produce human antibodies or analogs thereof. Further disclosed are methods by which the hosts are produced by multiple genetic modifications of embryonic cells in conjunction with breeding, as are methods for the recombination of the human loci randomly or at analogous host loci. Chimeric and transgenic mammals, particularly mice, are provided, having stably integrated large, xenogeneic DNA segments which are introduced by fusion with yeast spheroplasts comprising yeast artificial chromosomes which include the xenogeneic DNA segments and a selective marker such as HPRT, as well as embryonic stem cells.
Abstract:The subject invention provides non-human mammalian hosts characterized by inactivated endogenous Ig loci and functional human Ig loci for response to an immunogen to produce human antibodies or analogs thereof. The hosts are produced by multiple genetic modifications of embryonic cells in conjunction with breeding. Different strategies are employed for recombination of the human loci randomly or at analogous host loci. Chimeric and transgenic mammals, particularly mice, are provided, having stably integrated large, xenogeneic DNA segments. The segments are introduced by fusion with yeast spheroplasts comprising yeast artificial chromosomes (YACs) which include the xenogeneic DNA segments and a selective marker such as HPRT, and embryonic stem cells.
US Patent Website:Click Here for Full Text of Patent
Title Number:US6673986
Application Number:US1993000031801
Date Filed:15/03/1993
Date Published:06/01/2004
Assignee:Abgenix, Inc., Fremont, CA, USA


 
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