Genetically modified mice having humanized TCR variable genes
AssigneeRegeneron Pharmaceuticals, Inc.
InventorsLynn MacDonald, Andrew J. Murphy, John McWhirter, Naxin Tu, Vera Voronina, Cagan Gurer, Karolina Meagher, Sean Stevens
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Abstract
The invention provides a genetically modified non-human animal that comprises in its genome unrearranged T cell receptor variable gene loci, as well as embryos, cells, and tissues comprising the same. Also provided are constructs for making said genetically modified non-human animal and methods of making the same. Various methods of using the genetically modified non-human animal are also provided.
Claims42
A genetically modified mouse whose genome comprises:
- a replacement of an endogenous T cell receptor (TCR) variable α (Vα)gene with unarranged human TCR Vα segments and unrearranged human TCR Jα gene segments, wherein the unrearranged human TCR Vα and Jα gene segments are operably linked to a mouse TCR constant α (Cα) gene.
A genetically modified mouse whose genome comprises:
- a replacement of an endogenous T-cell receptor (TCR) variable β (Vβ) gene with unrearranged human TCR Vβ gene segments, unrearranged human TCR Dβ gene segments, and unrearranged human TCR Jβ gene segments, wherein the unrearranged human TCR Vβ, Dβ, and Jβ gene segments are operably linked to a mouse TCR constant β(Cβ) gene.
A genetically modified mouse whose genome comprises:
- a) a replacement of an endogenous T-cell receptor (TCR) variable a (Vα) gene with unrearranged human TCR Vα gene segments and unrearranged human TCR Jα gene segments, wherein the unrearranged human TCR Vα and Jα gene segments are operably linked to a mouse TCR constant α (Cα) gene;
- and
- b) a replacement of an endogenous T-cell receptor (TCR) variable β (Vβ) gene with unrearranged human TCR Vβ gene segments, unrearranged human TCR Dβ gene segments, and unrearranged human TCR Jβ gene segments, wherein the unrearranged human TCR Vβ, Dβ, and Jβ gene segments are operably linked to a mouse TCR constant β (Cβ) gene.
A method for making a genetically modified mouse comprising:
- a) replacing an endogenous T-cell receptor (TCR) variable α (Vα) gene with unrearranged human TCR Vα gene segments and unrearranged human TCR Jα gene segments, wherein the unrearranged human TCR Vα and Jα gene segments are operably linked to a mouse TCR constant α (Cα) gene;
- and
- b) replacing an endogenous TCR variable β (Vβ) gene with unrearranged human TCR Vβ gene segments, unrearranged human TCR Dβ gene segments, and unrearranged human TCR Jβ gene segments, wherein the unrearranged human TCR Vβ, Dβ, and Jβ gene segments are operably linked to a mouse TCR constant β (Cβ) gene.
A genetically modified mouse whose genome comprises:
- a) a replacement of an endogenous T-cell receptor (TCR) variable α (Vα) gene with a complete repertoire of unrearranged human TCR Vα gene segments and a complete repertoire of unrearranged human TCR Jα gene segments, wherein the unrearranged human TCR Vα and Jα gene segments are operably linked to a mouse TCR constant α (Cα) gene;
- and
- b) a replacement of an endogenous T-cell receptor (TCR) variable β (Vβ) gene with a complete repertoire of unrearranged human TCR Vβ gene segments, a complete repertoire of unrearranged human TCR Dβ gene segments, and a complete repertoire of unrearranged human TCR Jβ gene segments, wherein the unrearranged human TCR Vβ, Dβ, and Jβ gene segments are operably linked to a mouse TCR constant β (Cβ) gene.
Dependencies are inferred from the claim text.