Non-human animals having a humanized programmed cell death 1 gene
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 may be described, in some embodiments, as having 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).
1. A mouse whose genome comprises a humanized Programmed cell death 1 (Pdcd1) gene at an endogenous Pdcd1 locus, wherein the humanized Pdcd1 gene is operably linked to a Pdcd1 promoter and expresses a humanized Programmed cell death 1 (PD-1) polypeptide on the surface of activated T cells in said mouse and wherein said humanized PD-1 polypeptide comprises the N-terminal immunoglobulin V domain of a human PD-1 polypeptide and the intracellular domain of an endogenous mouse PD-1 polypeptide.
2. The mouse of claim 1 , wherein the humanized PD-1 polypeptide is translated in a cell of the mouse with a mouse signal peptide.
3. The mouse of claim 1 , wherein the humanized PD-1 polypeptide comprises the transmembrane sequence of the endogenous PD-1 polypeptide.
4. The mouse of claim 1 , wherein the humanized PD-1 polypeptide comprises amino acids 35-145, 27-145, or 26-169 of a human PD-1 polypeptide.
5. The mouse of claim 1 , wherein the humanized Pdcd1 gene comprises endogenous Pdcd1 exons 1, 4 and 5.
6. The mouse of claim 5 , wherein the humanized Pdcd1 gene further comprises an endogenous Pdcd1 exon 3 in whole or in part.
7. The mouse of claim 5 , wherein the humanized Pdcd1 gene comprises exon 2 of a human Pdcd1 gene.
8. The mouse of claim 7 , wherein the humanized Pdcd1 gene further comprises a human Pdcd1 exon 3 in whole or in part.
9. The mouse of claim 1 wherein the Pdcd1 promoter is a rodent Pdcd1 promoter.
10. The mouse of claim 1 , wherein the Pdcd1 promoter is an endogenous mouse Pdcd1 promoter.
11. The mouse of claim 1 , wherein the humanized Pdcd1 gene comprises exon 2 of a human Pdcd1 gene.
12. The mouse of claim 11 , wherein the humanized Pdcd1 gene further comprises a human Pdcd1 exon 3 in whole or in part.
13. The mouse of claim 12 , wherein the humanized Pdcd1 gene comprises the nucleotide sequence as set forth in SEQ ID NO: 23.
14. The mouse of claim 1 , wherein the mouse is homozygous for the humanized Pdcd1 gene.
15. The mouse of claim 1 , wherein the mouse does not detectably express a full-length endogenous mouse PD-1 polypeptide.
16. A humanized PD-1 polypeptide produced by the mouse of claim 15 .