Loading patent…
AssigneeRegeneron Pharmaceuticals, Inc.
InventorsSean Stevens, Andrew J. Murphy, Richard Flavell, Elizabeth Eynon, Jorge Galan, Tim Willinger, Markus Manz, Anthony Rongvaux, George D. Yancopoulos
Estimating the term…
A mouse with a humanization of the mIL-3 gene and the mGM-CSF gene, a knockout of a mRAG gene, and a knockout of a mIl2rg subunit gene; and optionally a humanization of the TPO gene is described. A RAG/Il2rg KO/hTPO knock-in mouse is described. A mouse engrafted with human hematopoietic stem cells (HSCs) that maintains a human immune cell (HIC) population derived from the HSCs and that is infectable by a human pathogen, e.g., S. typhi or M. tuberculosis is described. A mouse that models a human pathogen infection that is poorly modeled in mice is described, e.g., a mouse that models a human mycobacterial infection, wherein the mouse develops one or more granulomas comprising human immune cells. A mouse that comprises a human hematopoietic malignancy that originates from an early human hematopoietic cells is described, e.g., a myeloid leukemia or a myeloproliferative neoplasia.
A method comprising:
A second mouse comprising an engraftment of human CD34+hematopoietic cells isolated from a genetically modified first mouse, wherein each of the first mouse and the second mouse are null for a recombination-activating gene 2 (RAG2) gene and null for a mouse interleukin 2 receptor gamma (IL-2Rg) gene, wherein the genetically modified first mouse comprises an engraftment of human CD34+hematopoietic cells and a replacement of each allele of the mouse thrombopoietin (TPO) genes with a human TPO gene at the mouse TPO gene locus, wherein the genetically modified first mouse does not express mouse TPO, and wherein the engraftment of human CD34+hematopoietic cells isolated from the genetically modified first mouse results in a statistically significant increase in human CD45+ hematopoietic cells in the bone marrow of the second mouse relative to human CD45+ hematopoietic cells in a RAG2-null IL-2Rg-null fourth mouse engrafted with human CD34+hematopoietic cells isolated from a RAG2-null IL-2Rg-null third mouse, wherein the RAG2-null IL-2Rg-null third mouse comprises an engraftment of human CD34+ hematopoietic cells and expresses mouse TPO.
Dependencies are inferred from the claim text.