Non-human animals having a humanized signal-regulatory protein gene
AssigneeRegeneron Pharmaceuticals, Inc.
InventorsAndrew J. Murphy, O. Gavin Thurston, Bindu Varghese, Cagan Gurer
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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.
Claims18
A mouse whose genome comprises a humanized SIRPα gene at an endogenous mouse SIRPα locus, wherein the humanized SIRPα gene
- (i) comprises exon 1 of a mouse SIRPα gene, exons 2, 3 and 4 of a human SIRPα gene, and exons 5, 6, 7 and 8 of the mouse SIRPα gene,
- (ii) is operably linked to a mouse SIRPα promoter at the endogenous mouse SIRPα locus, and
- (iii) expresses in the mouse a humanized SIRPα protein comprising an extracellular portion of the human SIRPα protein encoded by the human SIRPα gene and an intracellular portion of the mouse SIRPα protein encoded by the mouse SIRPα gene;
- and wherein the mouse is homozygous for the humanized SIRPα gene.
A mouse embryonic stem (ES) cell, comprising a humanized SIRPαgene at an endogenous mouse SIRPα locus, wherein the humanized SIRPα gene
- (i) comprises exon 1 of a mouse SIRPα gene, exons 2, 3 and 4 of a human SIRPα gene, and exons 5, 6, 7 and 8 of the mouse SIRPα gene,
- (ii) is operably linked to a mouse SIRPα promoter at the endogenous mouse SIRPα locus, and
- (iii) encodes a humanized SIRPα protein comprising an extracellular portion of the human SIRPα protein encoded by the human SIRPα gene and an intracellular portion of the mouse SIRPα protein encoded by the mouse SIRPα gene.
A method of making a mouse, comprising
- (a) modifying an endogenous mouse SIRPα locus in a mouse ES cell such that the modified SIRPα locus comprises a humanized SIRPα gene, wherein the humanized SIRPα gene
- (i) comprises exon 1 of a mouse SIRPα gene, exons 2, 3 and 4 of a human SIRPα gene, and exons 5, 6, 7 and 8 of the mouse SIRPα gene,
- (ii) is operably linked to a mouse SIRPα promoter at the endogenous mouse SIRPα locus, and
- (iii) encodes a humanized SIRPα protein comprising an extracellular portion of the human SIRPα protein encoded by the human SIRPα gene and an intracellular portion of the mouse SIRPα protein encoded by the mouse SIRPα gene;
- (b) obtaining a mouse ES cell comprising the modified SIRPα locus;
- and
- (c) creating a mouse using the mouse ES cell of step (b).
Dependencies are inferred from the claim text.