Mice that make heavy chain antibodies
First Claim
1. A transgenic mouse comprising a germline modification, which modification comprises:
- (a) a deletion of a nucleic acid sequence encoding a CH1 domain of an endogenous IgG constant region gene; and
(b) an inclusion of one or more human heavy chain variable region gene segments, wherein the one or more human heavy chain variable region gene segments is operably linked to the endogenous IgG constant region of (a);
wherein the mouse comprises an intact IgM constant region gene and wherein the mouse expresses an IgG heavy chain antibody comprising a human variable domain, lacking a CH1 domain, in whole or in part, and lacking a cognate light chain and secretes said IgG heavy chain antibody into its serum.
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Abstract
Genetically modified non-human animals and methods and compositions for making and using them are provided, wherein the genetic modification comprises a deletion in an immunoglobulin constant region CH1 gene (optionally a deletion in a hinge region) of an IgG, IgA, IgD, and/or IgE, and wherein the mouse is capable of expressing a functional IgM. Genetically modified mice are described, including mice having a functional IgM gene and modified to have a deletion of a CH1 domain and a hinge region in a heavy chain constant domain that is not an IgM, e.g., in an IgG heavy chain constant domain. Genetically modified mice that make human variable/mouse constant chimeric heavy chain antibodies (antibodies that lack a light chain), fully mouse heavy chain antibodies, or fully human heavy chain antibodies are provided.
97 Citations
14 Claims
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1. A transgenic mouse comprising a germline modification, which modification comprises:
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(a) a deletion of a nucleic acid sequence encoding a CH1 domain of an endogenous IgG constant region gene; and (b) an inclusion of one or more human heavy chain variable region gene segments, wherein the one or more human heavy chain variable region gene segments is operably linked to the endogenous IgG constant region of (a); wherein the mouse comprises an intact IgM constant region gene and wherein the mouse expresses an IgG heavy chain antibody comprising a human variable domain, lacking a CH1 domain, in whole or in part, and lacking a cognate light chain and secretes said IgG heavy chain antibody into its serum. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14)
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Specification