Humanized IL-6 and IL-6 receptor

摘要

Mice that comprise a replacement of endogenous mouse IL-6 and/or IL-6 receptor genes are described, and methods for making and using the mice. Mice comprising a replacement at an endogenous IL-6Rα locus of mouse ectodomain-encoding sequence with human ectodomain-encoding sequence is provided. Mice comprising a human IL-6 gene under control of mouse IL-6 regulatory elements is also provided, including mice that have a replacement of mouse IL-6-encoding sequence with human IL-6-encoding sequence at an endogenous mouse IL-6 locus.

主权项

1. A genetically modified rodent animal, wherein the genome of said rodent animal comprises a replacement at an endogenous rodent IL-6 locus of a rodent gene encoding IL-6 with a human gene encoding human IL-6, wherein the human gene encoding human IL-6 is under control of endogenous rodent regulatory elements at the endogenous rodent IL-6 locus and is expressed, and the replaced rodent IL-6 gene is not expressed; wherein the genome of said rodent animal further comprises a replacement at an endogenous rodent IL-6Rα locus of a rodent nucleic acid encoding a rodent IL-6Rα ectodomain with a human nucleic acid encoding a human IL-6Rα ectodomain to form a humanized IL-6Rα gene, wherein the humanized IL-6Rα gene is under control of endogenous rodent regulatory elements at the endogenous rodent IL-6Rα locus, wherein the humanized IL-6Rα gene is expressed and encodes a humanized IL-6Rα protein which comprises said human IL-6Rα ectodomain and rodent IL-6Rα transmembrane and cytoplasmic domains; and wherein the rodent animal exhibits an acute phase response to an acute phase inducer and is a rat or a mouse.