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 mouse, whose genome comprises a humanization of an endogenous mouse IL-6Rα gene at an endogenous mouse IL-6Rα locus, wherein the humanization comprises a replacement of a mouse IL-6Rα ectodomain-encoding nucleic acid with a human IL-6Rα ectodomain-encoding nucleic acid to form a humanized IL-6Rα gene, wherein the humanized IL-6Rα gene is under control of endogenous mouse regulatory elements at the endogenous mouse 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 mouse IL-6Rα transmembrane and cytoplasmic domains, and wherein said genetically modified mouse does not express a fully mouse IL-6Rα and lacks an acute phase response to an acute phase inducer.