US 8,847,004 B2 · Humanized M-CSF mice

Abstract

Genetically modified mice comprising a nucleic acid sequence encoding a human M-CSF protein are provided. Also provided are genetically modified mice comprising a nucleic acid sequence encoding a human M-CSF protein that have been engrafted with human cells such as human hematopoietic cells, and methods for making such engrafted mice. These mice find use in a number of applications, such as in modeling human immune disease and pathogen infection; in in vivo screens for agents that modulate hematopoietic cell development and/or activity, e.g. in a healthy or a diseased state; in in vivo screens for agents that are toxic to hematopoietic cells; in in vivo screens for agents that prevent against, mitigate, or reverse the toxic effects of toxic agents on hematopoietic cells; in in vivo screens of human hematopoietic cells from an individual to predict the responsiveness of an individual to a disease therapy, etc.

Claims16

Dependent claims

A humanized M-CSF mouse, comprising:

a Rag2 gene knock-out;
an IL2rg gene knock-out;
a nucleic acid sequence incorporated into the genome of the humanized M-CSF mouse, which sequence encodes a human M-CSF protein and is operably linked to the endogenous promoter of the mouse M-CSF gene at the mouse M-CSF locus;
wherein the mouse expresses M-CSF RNA encoded by the nucleic acid sequence in bone marrow, spleen, blood, liver, brain, testis and kidney.

1 more element

A mouse model of the human hematopoietic system, comprising:

(a) a mouse which comprises:
a Rag2 gene knock-out;
an IL2rg gene knock-out;
a nucleic acid sequence incorporated into the genome of the mouse, which sequence encodes a human M-CSF protein and is operably linked to the endogenous promoter of the mouse M-CSF gene at the mouse M-CSF locus;
and
(b) human hematopoietic cells, wherein the mouse expresses M-CSF RNA encoded by the nucleic acid sequence in bone marrow, spleen, blood, liver, brain, lung, testis and kidney.

3 more elements

Dependencies are inferred from the claim text.

Facts

Application

13/372,787Filed 14 Feb 2012 · us provisional application

Priority

15 Feb 2011

Published

US 2013/0042330 A114 Feb 2013

Granted

30 Sep 2014

Term ends

Not estimatedThe source records don’t support an estimate.

Classification21 codes

A01K 67/0278
Genetically modified vertebrates, e.g. transgenic: knock-in vertebrates, e.g. humanised vertebrates
A01K 67/027
Rearing or breeding animals, not otherwise provided for; New or modified breeds of animals: new or modified breeds of vertebrates
A01K 67/0271
New or modified breeds of vertebrates: chimeric vertebrates, e.g. comprising exogenous cells
A61K 49/0008
Screening or testing of compounds for diagnosis of disorders, assessment of conditions, e.g. renal clearance, gastric emptying, testing for…:…

Humanized M-CSF mice

Life of this patent

Humanized M-CSF mice

Life of this patent

Abstract

Claims16