Regeneron Pharmaceuticals, Inc.

Li-Hsien Wang

Sean Stevens

Andrew J Murphy

Anthony T Dore, Jr

Yingzi Xue

Joel H Martin

Erin M Allison

Lynn Macdonald

Cagan Gurer

Naxin Tu

Stanley J Wiegand

Mark W Sleeman

Jingtai Cao

Hsin Chieh Lin

Jr Dore

Anthony T Dore

Non-human animals comprising a human or humanized IL-4 and/or IL-4Rα nucleic acid sequence are provided. Non-human animals that comprise a replacement of the endogenous IL-4 gene and/or IL-4Rα gene with a human IL-4 gene and/or IL-4Rα gene in whole or in part, and methods for making and using the non-human animals, are described. Non-human animals comprising a human or humanized IL-4 gene under control of non-human IL-4 regulatory elements is also provided, including non-human animals that have a replacement of non-human IL-4-encoding sequence with human IL-4-encoding sequence at an endogenous non-human IL-4 locus. Non-human animals comprising a human or humanized IL-4Rα gene under control of non-human IL-4Rα regulatory elements is also provided, including non-human animals that have a replacement of non-human IL-4Rα-encoding sequence with human or humanized IL-4Rα-encoding sequence at an endogenous non-human C IL-4Rα locus. Non-human animals comprising human or humanized IL-4 gene and/or IL-4Rα sequences, wherein the non-human animals are rodents, e.g., mice or rats, are provided.

Humanized IL-4 and IL-4Rα animals

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.

Humanized IL-6 and IL-6 receptor

Non-human animals comprising a human or humanized IL-4 and/or IL-4R&#x3b1; nucleic acid sequence are provided. Non-human animals that comprise a replacement of the endogenous IL-4 gene and/or IL-4R&#x3b1; gene with a human IL-4 gene and/or IL-4R&#x3b1; gene in whole or in part, and methods for making and using the non-human animals, are described. Non-human animals comprising a human or humanized IL-4 gene under control of non-human IL-4 regulatory elements is also provided, including non-human animals that have a replacement of non-human IL-4-encoding sequence with human IL-4-encoding sequence at an endogenous non-human IL-4 locus. Non-human animals comprising a human or humanized IL-4R&#x3b1; gene under control of non-human IL-4R&#x3b1; regulatory elements is also provided, including non-human animals that have a replacement of non-human IL-4R&#x3b1;-encoding sequence with human or humanized IL-4R&#x3b1;-encoding sequence at an endogenous non-human C IL-4R&#x3b1; locus. Non-human animals comprising human or humanized IL-4 gene and/or IL-4R&#x3b1; sequences, wherein the non-human animals are rodents, e.g., mice or rats, are provided.

Humanized IL-4 and IL-4Ra animals

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-6R&#x3b1; 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.

Non-human animals comprising a human or humanized IL-4 and/or IL-4R&#x3b1; nucleic acid sequence are provided. Non-human animals that comprise a replacement of the endogenous IL-4 gene and/or IL-4R&#x3b1; gene with a human IL-4 gene and/or IL-4R&#x3b1; gene in whole or in part, and methods for making and using the non-human animals, are described. Non-human animals comprising a human or humanized IL-4 gene under control of non-human IL-4 regulatory elements is also provided, including non-human animals that have a replacement of non-human IL-4-encoding sequence with human IL-4-encoding sequence at an endogenous non-human IL-4 locus. Non-human animals comprising a human or humanized IL-4R&#x3b1;, gene under control of non-human IL-4R&#x3b1; regulatory elements is also provided, including non-human animals that have a replacement of non-human IL-4R&#x3b1;-encoding sequence with human or humanized IL-4R&#x3b1;-encoding sequence at an endogenous non-human CIL-4R&#x3b1; locus. Non-human animals comprising human or humanized IL-4 gene and/or IL-4R&#x3b1;, sequences, wherein the non-human animals are rodents, e.g., mice or rats, are provided.

Humanized IL-4 and IL-4R&#x3b1; animals

Genetically modified non-human animals and methods and compositions for making and using them are provided, wherein the genetic modification comprises a deletion of the endogenous low affinity Fc&#x3b3;R locus, and wherein the mouse is capable of expressing a functional FcR&#x3b3;-chain. Genetically modified mice are described, including mice that express low affinity human Fc&#x3b3;R genes from the endogenous Fc&#x3b3;R locus, and wherein the mice comprise a functional FcR&#x3b3;-chain. Genetically modified mice that express up to five low affinity human Fc&#x3b3;R genes on accessory cells of the host immune system are provided.

Growing community of inventors

Somers, NY, United States of America

Li-Hsien Wang