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.
Claims21
A mouse whose genome comprises
- (a) an insertion of one or more human VH, one or more human DH, and one or more human JH gene segments upstream of an endogenous heavy chain constant region gene;
- and
- (b) an insertion of one or more human VL and one or more human JL gene segments upstream of an endogenous light chain constant region gene;
- and
- (c) an ectopic nucleic acid sequence that encodes an Adam6 protein that is functional in the mouse,
- 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:
- (A) 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;
- and
- (B) light chain variable domains encoded by the one or more human VL and one or more human JL gene segments linked to light chain constant domains encoded by the endogenous light chain constant region gene,
- wherein the antibodies specifically bind the antigen.
An isolated mouse cell whose genome comprises:
- (a) an insertion of one or more human VH, one or more human DH, and one or more human JH gene segments upstream of an endogenous heavy chain constant region;
- and
- (b) an insertion of one or more human VL and one or more human JL gene segments upstream of an endogenous light chain constant region;
- and
- (c) an ectopic nucleic acid sequence that encodes an Adam6 protein that is functional in the mouse.
Dependencies are inferred from the claim text.