Genetically modified mice having a humanized programmed cell death 1 gene
AssigneeRegeneron Pharmaceuticals, Inc.
InventorsElena Burova, Alexander O. Mujica, Ka-Man Venus Lai, Andrew J. Murphy
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Abstract
Non-human animals, and methods and compositions for making and using the same, are provided, wherein the non-human animals comprise a humanization of a Programmed cell death 1 (Pdcd1) gene. The non-human animals, in some embodiments, comprise a genetic modification to an endogenous Pdcd1 gene so that the non-human animals express a PD-1 polypeptide that includes a human portion and an endogenous portion (e.g., a non-human portion).
Claims19
A genetically modified mouse embryonic stem(ES) cell whose genome comprises a humanized Programmed cell death 1 (Pdcd1) gene comprising a replacement of exon 2 and at least part of exon 3 of an endogenous Pdcd1 gene with exon 2 and at least part of exon 3 of a human Pdcd1 gene, wherein expression of the humanized Pdcd1 gene is under the control of an endogenous Pdcd1 promoter, and the humanized Pdcd1 gene encodes a humanized PD-1 polypeptide comprising an N-terminal immunoglobulin variable (V) domain of a human PD-1 polypeptide and an intracellular domain of a mouse PD-1 polypeptide.
A method of making a genetically modified mouse embryonic stem(ES) cell, the method comprising:
- replacing exon 2 and at least part of exon 3 of an endogenous Programmed cell death 1 (Pdcd1) gene in a mouse ES cell with exon 2 and at least part of exon 3 of a human Pdcd1 gene such that a genetically modified mouse ES cell is obtained whose genome comprises a humanized Programmed cell death 1 (Pdcd1) gene comprising a replacement of exon 2 and at least part of exon 3 of the endogenous Pdcd1 gene with exon 2 and at least part of exon 3 of the human Pdcd1 gene, wherein expression of the humanized Pdcd1 gene is under the control of an endogenous Pdcd1 promoter, and the humanized Pdcd1 gene encodes a humanized PD-1 polypeptide comprising an N-terminal immunoglobulin variable (V) domain of a human PD-1 polypeptide and an intracellular domain of a mouse PD-1 polypeptide.
Dependencies are inferred from the claim text.