A transgenic mouse that expresses a diversity of human sequence heavy and light chain immunoglobulins.

Abstract:

:We have generated transgenic mice that express a diverse repertoire of human sequence immunoglobulins. The expression of this repertoire is directed by light and heavy chain minilocus transgenes comprised of human protein coding sequences in an unrearranged, germ-line configuration. In this paper we describe the construction of these miniloci and the composition of the CDR3 repertoire generated by the transgenic mice. The largest transgene discussed is a heavy chain minilocus that includes human mu and gamma 1 coding sequences together with their respective switch regions. It consists of a single 61 kb DNA fragment propagated in a bacterial plasmid vector. Both human heavy chain classes are expressed in animals that carry the transgene. In light chain transgenic animals the unrearranged minilocus sequences recombine to form VJ joints that use all five human J kappa segments, resulting in a diversity of human-like CDR3 regions. Similarly, in heavy chain transgenics the inserted sequences undergo VDJ joining complete with N region addition to generate a human-like VH CDR3 repertoire. All six human JH segments and at least eight of the ten transgene encoded human D segments are expressed. The transgenic animals described in this paper represent a potential source of human sequence antibodies for in vivo therapeutic applications.

journal_name

Nucleic Acids Res

journal_title

Nucleic acids research

authors

Taylor LD,Carmack CE,Schramm SR,Mashayekh R,Higgins KM,Kuo CC,Woodhouse C,Kay RM,Lonberg N

doi

10.1093/nar/20.23.6287

keywords:

subject

Has Abstract

pub_date

1992-12-11 00:00:00

pages

6287-95

issue

23

eissn

0305-1048

issn

1362-4962

journal_volume

20

pub_type

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