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Transgenic animals that carry human Ig light chain genes
专利权人:
Amgen Fremont Inc.
发明人:
Green, Larry L.,Ivanov, Vladimir
申请号:
ES10178127
公开号:
ES2645698T3
申请日:
2002.11.27
申请国别(地区):
ES
年份:
2017
代理人:
摘要:
Production method of a transgenic mouse expressing human Ig-κ light chains and human Ig-λ light chains, comprising the steps of: (A) producing a mouse embryonic stem cell (ES) comprising a λ light chain locus human, in the germline configuration, and stably integrated into the genome of the ES cell, in which said λ light chain locus comprises the Vλ gene segments from 5 'of the Vκ gene 1-27 to 3 'of the enhancer of λ in 3'; (B) produce a transgenic mouse from the ES cell of step (A); and (C) matching said transgenic mouse of step (B) with a transgenic mouse whose genome comprises: (i) a stably integrated part of a human κ light chain locus in the germline configuration, wherein said part comprises the genes of Vκ beginning in Vκ-B3 and ending in Vκ-OP11, with a deletion of Vκ-LP13 to Vκ-LP6; the Jκ region; the Cκ region; the element of deletion of κ; and the 3 'and intronic enhancers of lgκ; and (ii) a stably integrated part of a human immunoglobulin heavy chain locus in the germline configuration, wherein said part comprises the VH genes starting at VH6-1 and ending at VH3-65: the region DH, the JH region, the genes of the Cμ constant region, the genes of the Cδ constant region, the genes of the Cγ constant region, the 3 'mouse enhancer and the human intronic enhancer, in which said genes of the Cγ constant region are selected from the group consisting of: genes from the human Cγ1 constant region, genes from the human Cγ2 constant region and genes from the human Cγ4 constant region; (iii) homozygous inactivated endogenous immunoglobulin heavy chain loci; and (iv) homozygous inactivated endogenous immunoglobulin κ light chain loci; to produce a transgenic mouse as offspring whose genome comprises: (a) said human λ light chain locus, in the germline configuration, and stably integrated; (b) said stably integrated part of a human κ light chain locus in the germline configuration: (c) said stably integrated part of a human immunoglobulin heavy chain locus in the germli
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