Non-human animals having a humanized signal-regulatory protein gene
AssigneeRegeneron Pharmaceuticals, Inc.
InventorsAndrew J. Murphy, O. Gavin Thurston, Bindu Varghese, Cagan Gurer
Life of this patent
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Abstract
Genetically modified non-human animals and methods and compositions for making and using the same are provided, wherein the genetic modification comprises a humanization of an endogenous signal-regulatory protein gene, in particular a humanization of a SIRPα gene. Genetically modified mice are described, including mice that express a human or humanized SIRPα protein from an endogenous SIRPα locus.
Claims32
1-19. (canceled)
A method of making a mouse that expresses a SIRPα protein from an endogenous SIRPα locus, wherein the SIRPα protein comprises a human sequence, the method comprising:
- (a) targeting an endogenous SIRPα locus in a mouse ES cell with a genomic fragment comprising a nucleotide sequence that encodes a human SIRPα protein in whole or in part;
- (b) obtaining a modified mouse ES cell comprising an endogenous SIRPα locus that comprises the human sequence of (a);
- and,
- (c) creating a mouse using the modified ES cell of (b).
23-25. (canceled)
A method of engrafting human cells into a mouse, comprising steps of:
- (a) providing a mouse whose genome comprises a SIRPα gene that encodes an extracellular portion of a human SIRPα protein linked to an intracellular portion of a mouse SIRPα protein;
- and
- (b) transplanting one or more human cells into the mouse.
33-34. (canceled)
A method comprising,
- (a) providing one or more cells whose genome includes a SIRPα gene that encodes an extracellular portion of a human SIRPα protein linked to an intracellular portion of a mouse SIRPα protein;
- (b) incubating the one or more cells of step (a) with a labeled substrate;
- and
- (c) measuring phagocytosis of the labeled substrate by the one or more cells of step (b).
(canceled)
(canceled)
A method comprising,
- (a) providing a mouse whose genome includes a SIRPα gene that encodes an extracellular portion of a human SIRPα protein linked to an intracellular portion of a mouse SIRPα protein;
- (b) exposing the mouse to an antigen;
- and
- (c) measuring phagocytosis of the antigen by one or more cells of the mouse.
A method of assessing the therapeutic efficacy of a drug targeting human cells, comprising:
- providing a mouse whose genome comprises a SIRPα gene that encodes an extracellular portion of a human SIRPα protein linked to an intracellular portion of a mouse SIRPα protein;
- transplanting one or more human cells into the mouse;
- administering a drug candidate to said mouse;
- and
- monitoring the human cells in the mouse to determine the therapeutic efficacy of the drug candidate.
Dependencies are inferred from the claim text.