Genetically Modified Major Histocompatibility Complex Animals

摘要

The invention provides genetically modified non-human animals that express a humanized MHC II protein (humanized MHC II α and β polypeptides), 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 non-human animal comprising at an endogenous MHC II gene locus (a) a first and second nucleotide sequence, each respectively encoding a first chimeric human/non-human MHC II α polypeptide and a first chimeric human/non-human MHC II β polypeptide, which together form a first functional MHC II complex,
(b) a third and fourth nucleotide sequence, each respectively encoding a second chimeric human/non-human MHC II α polypeptide and a second chimeric human/non-human MHC II β polypeptide, which together form a second functional MHC II complex, wherein a human portion of each chimeric human/non-human MHC II α polypeptide comprises a human MHC II α extracellular domain and a human portion of each chimeric human/non-human MHC II β polypeptide comprises a human MHC II β extracellular domain, and wherein the first and second functional MHC II complexes comprise different human MHC II extracellular domains.