Humanized FcgR Mice
AssigneeRegeneron Pharmaceuticals, Inc.
InventorsLynn Macdonald, Naxin Tu, Cagan Gurer, Li-Hsien Wang, Sean Stevens, Andrew J. Murphy
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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 of the endogenous low affinity FcγR locus, and wherein the mouse is capable of expressing a functional FcRγ-chain. Genetically modified mice are described, including mice that express low affinity human FcγR genes from the endogenous FcγR locus, and wherein the mice comprise a functional FcRγ-chain. Genetically modified mice that express up to five low affinity human FcγR genes on accessory cells of the host immune system are provided.
Claims21
An isolated lymphocyte comprising a contiguous human nucleotide sequence that encodes at least two α-chains of an FcγR selected from FcγRIIA, FcγRIIB, FcγRIIC, FcγRIIIA, FcγRIIIB, and a combination thereof;
- wherein the at least two α-chains are transcribed from a mouse FcγR locus in which the human nucleotide sequence replaces mouse FcγR sequences, and wherein the mouse comprises a functional FcR γ-chain gene.
A method for measuring a level of mouse cells that bear a human antigen, comprising
- (a) administering to a mouse an agent that comprises a human Fc or fragment thereof that binds a human FcγRIIIA, wherein the mouse
- (i) expresses a mouse FcγR γ-chain,
- (ii) expresses an α-chain of a human FcγRIIA,
- (iii) expresses an α-chain of a human FcγRIIIA on an NK cell,
- (iv) lacks a nucleotide sequence that encodes an α-chain of a mouse FcγR;
- wherein the mouse comprises a mouse cell that bears on its surface a human antigen that is not a human FcγR α-chain, and wherein the agent binds the human antigen with a KD of 10−6 or lower;
- and,
- (b) measuring a level of the mouse cells that bear the human antigen at one or more time points following administration of the agent.
Dependencies are inferred from the claim text.