ADAM6 mice
AssigneeRegeneron Pharmaceuticals, Inc.
InventorsLynn MacDonald, Sean Stevens, Andrew J. Murphy
Life of this patent
Estimating the term…
Abstract
Mice are provided that comprise a reduction or deletion of ADAM6 activity from an endogenous ADAM6 locus, or that lack an endogenous locus encoding a mouse ADAM6 protein, wherein the mice comprise a sequence encoding an ADAM6 or ortholog or homolog or fragment thereof that is functional in a male mouse. In one embodiment, the sequence is an ectopic ADAM6 sequence or a sequence that confers upon a male mouse the ability to generate offspring by mating. Mice and cells with genetically modified immunoglobulin heavy chain loci that comprise an ectopic nucleotide sequence encoding a mouse ADAM6 or functional fragment or homolog or ortholog thereof are also provided.
Claims23
A genetically modified mouse whose genome comprises:
- (a) ectopic placement of an ADAM6 gene;
- and
- (b) a human immunoglobulin heavy chain variable region locus comprising an insertion of one or more human VH gene segments, one or more human DH gene segments, and one or more human JH gene segments into the endogenous mouse heavy chain locus, wherein the human VH, DH and JH gene segments are operably linked to a heavy chain constant region gene;
- so that the mouse is characterized in that:
- (i) it is fertile;
- and
- (ii) when it is immunized with an antigen, it generates antibodies comprising heavy chain variable domains encoded by the one or more human VH, one or more human DH, and one or more human JH gene segments, linked to heavy chain constant domains encoded by the heavy chain constant region gene, wherein the antibodies show specific binding to the antigen.
An isolated mouse cell whose genome comprises:
- (a) ectopic placement of an ADAM6 gene;
- and
- (b) a human immunoglobulin heavy chain variable region locus comprising an insertion of one or more human VH gene segments, one or more human DH gene segments, and one or more human JH gene segments into the endogenous heavy chain locus, wherein the human VH, DH and JH gene segments are operably linked to a heavy chain constant region gene.
Dependencies are inferred from the claim text.