Humanized Fc gamma R mice
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 FcγR locus, and wherein the mouse is capable of expressing a functional FcRγ-chain. Genetically modified mice are described, including mice that express low affinity human FcγR genes from the endogenous FcγR locus, and wherein the mice comprise a functional FcRγ-chain. Genetically modified mice that express up to five low affinity human FcγR genes on accessory cells of the host immune system are provided.
1. A genetically modified mouse embryonic stem (ES) cell whose genome comprises at least two low affinity human FcγR α-chain genes that replace the endogenous mouse low affinity FcγR α-chain genes, wherein the mouse ES cell comprises a functional endogenous FcR γ-chain gene.
2. The genetically modified mouse ES cell of claim 1 , wherein the at least two low affinity human FcγR α-chain genes are selected from the group consisting of a human FcγRIIA α-chain gene, a human FcγRIIB α-chain gene, a human FcγRIIC α-chain gene, a human FcγRIIIA α-chain gene and a human FcγRIIIB α-chain gene.
3. The genetically modified mouse ES cell of claim 1 , wherein the at least two low affinity human FcγR α-chain genes are a human FcγRIIA α-chain gene and a human FcγRIIIA α-chain gene.
4. The genetically modified mouse ES cell of claim 1 , wherein the genome of the mouse ES cell comprises a human FcγRIIB α-chain gene, a human FcγRIIC α-chain gene, and a human FcγRIIIB α-chain gene.
5. A mouse embryo comprising the ES cell of claim 1 .
6. A method of making a genetically modified mouse comprising:
obtaining the genetically modified mouse ES cell of claim 1 ;
transplanting the genetically modified ES cell into a recipient mouse embryo; and
obtaining a genetically modified mouse whose genome comprises at least two low affinity human FcγR α-chain genes that replace the endogenous low affinity FcγR α-chain genes and a functional endogenous FcR γ-chain gene.
7. The method of claim 6 , wherein the endogenous low affinity FcγR α-chain genes are replaced with a human FcγRIIA α-chain gene and a human FcγRIIIA α-chain gene.
8. The method of claim 6 , wherein the endogenous low affinity FcγR α-chain genes are replaced with a human FcγRIIB α-chain gene, a human FcγRIIC α-chain gene, and a human FcγRIIIB α-chain gene.
9. The method of claim 6 , wherein the endogenous low affinity FcγR α-chain genes are replaced with a human FcγRIIA α-chain gene, a human FcγRIIB α-chain gene, a human FcγRIIC α-chain gene, a human FcγRIIIA α-chain gene and a human FcγRIIIB α-chain gene.
10. A genetically modified mouse embryonic stem (ES) cell whose genome comprises a human FcγRIIIA α-chain gene that replaces the endogenous FcγRIIB, FcγRIII, and FcγRIV α-chain genes, wherein the mouse ES cell comprises a functional endogenous FcRγ-chain gene.
11. A mouse embryo comprising the ES cell of claim 10 .
12. A method of making a genetically modified mouse comprising:
obtaining the genetically modified mouse ES cell of claim 10 ;
transplanting the genetically modified ES cell into a recipient mouse embryo; and
obtaining a genetically modified mouse whose genome comprises a human FcγRIIIA α-chain gene that replaces the endogenous FcγRIIB, FcγRIII, and FcγRIV α-chain genes and a functional endogenous FcR γ-chain gene.
13. A method for making a genetically modified mouse embryonic stem (ES) cell whose genome comprises at least two low affinity human FcγR α-chain genes and a functional endogenous FcR γ-chain gene, the method comprising
replacing an endogenous low affinity FcγR α-chain genes in the genome of a mouse ES cell with at least two low affinity human FcγR α-chain genes such that a genetically modified mouse ES cell whose genome comprises at least two low affinity human FcγR α-chain genes and a functional endogenous FcR γ-chain is obtained.