Genetically modified major histocompatibility complex mice

摘要

The invention provides genetically modified non-human animals that express chimeric human/non-human MHC I polypeptide and/or human or humanized β2 microglobulin polypeptide, as well as embryos, cells, and tissues comprising the same. Also provided are constructs for making said genetically modified animals and methods of making the same. Methods of using the genetically modified animals to study various aspects of human immune system are provided.

主权项

1. A mouse whose genome comprises at an endogenous H-2K locus a nucleotide sequence encoding a chimeric human/mouse HLA-A/H-2K polypeptide, wherein the nucleotide sequence is in operable linkage with an endogenous mouse regulatory element and is operably linked to a MHC class I leader encoding sequence,
wherein the nucleotide sequence comprises from 5′ to 3′ (i) a first nucleic acid sequence that encodes the α1, α2 and α3 domains of the human HLA-A polypeptide, which first nucleic acid sequence replaces a sequence encoding the α1, α2, and α3 domains of the mouse H-2K polypeptide at the mouse H-2K locus and (ii) a second nucleic acid sequence that encodes the transmembrane and cytoplasmic domains of the mouse H-2K polypeptide, wherein the mouse expresses, on the surface of nucleated cells, from the endogenous H-2K locus the chimeric human/mouse HLA-A/H-2K polypeptide that comprises the α1, α2 and α3 domains of the human HLA-A polypeptide and the transmembrane and cytoplasmic domains of the mouse H-2K polypeptide.