Yale University

Regeneron Pharmaceuticals, Inc.

Institute for Research in Biomedicine (irb)

Institute for Research in Biomedicine

Till Strowig

Richard A Flavell

Markus G Manz

Andrew J Murphy

George D Yancopoulos

Sean Stevens

Anthony Rongvaux

Madhav Dhodapkar

Chiara Borsotti

Cagan Gurer

Tim Willinger

Noah Palm

Marcel De Zoete

Liang Shan

Dietmar Herndler-Brandstetter

Davor Frleta

Elizabeth Eynon

William Philbrick

Noah W Palm

Markus Gabriel Manz

The invention relates generally to genetically modified non-human animals expressing human polypeptides and their methods of use.

Genetically modified non-human animals and methods of use thereof

Genetically modified non-human animals are provided that may be used to model human hematopoietic cell development, function, or disease. The genetically modified non-human animals comprise a nucleic acid encoding human IL-6 operably linked to an IL-6 promoter. In some instances, the genetically modified non-human animal expressing human IL-6 also expresses at least one of human M-CSF, human IL-3, human GM-CSF, human SIRPa or human TPO. In some instances, the genetically modified non-human animal is immunodeficient. In some such instances, the genetically modified non-human animal is engrafted with healthy or diseased human hematopoietic cells. Also provided are methods for using the subject genetically modified non-human animals in modeling human hematopoietic cell development, function, and/or disease, as well as reagents and kits thereof that find use in making the subject genetically modified non-human animals and/or practicing the subject methods.

Genetically modified non-human animals expressing human SIRP&#x3b1; and human IL-15 from the non-human animal genome are provided. Also provided are methods for making non-human animals expressing human SIRP&#x3b1; and human IL-15 from the non-human animal genome, and methods for using non-human animals expressing human SIRP&#x3b1; and human IL-15 from the non-human animal genome. These animals and methods find many uses in the art, including, for example, in modeling human T cell and/or natural killer (NK) cell development and function, in modeling human pathogen infection of human T cells and/or NK cells, and in various in vivo screens.

The invention relates generally to compositions and methods of using transgenic non-human animals expressing human SIRP&#x3b1; that are engrafted with a human hematopoietic system. In various embodiments, the human hematopoietic system engrafted, human SIRP&#x3b1; transgenic non-human animals of the invention are useful as systems for the in vivo evaluation of the growth and differentiation of hematopoietic and immune cells, for the in vivo assessment of an immune response, for the in vivo evaluation of vaccines and vaccination regimens, for in vivo production and collection of immune mediators, including human antibodies, and for use in testing the effect of agents that modulate hematopoietic and immune cell function.

Human SIRP&#x3b1; transgenic mice and their methods of use

Human SIRPAalpha transgenic animals and their methods of use

Growing community of inventors

Braunschweig, Germany

Till Strowig