Immunodeficient non-human animal
The present disclosure relates to the genetically modified non-human animals that have a disruption at the endogenous CD132 gene (e.g., CD132 knockout), and methods of use thereof.
1. A genetically-modified mouse or a progeny thereof, whose genome comprises a disruption in the mouse's endogenous CD132 gene, wherein the disruption of the endogenous CD132 gene comprises
deletion of more than 150 nucleotides in exon 1;
deletion of the entirety of intron 1, exon 2, intron 2, exon 3, intron 3, exon 4, intron 4, exon 5, intron 5, exon 6, intron 6, exon 7, intron 7; and
deletion of more than 250 nucleotides in exon 8,
wherein the disruption is performed by CRISPR associated protein 9 (Cas9) with sgRNAs that target SEQ ID NO: 3 and SEQ ID NO: 6.
2. A method of producing a genetically-modified mouse, the method comprising
introducing CRISPR associated protein 9 (Cas9) or a nucleic acid encoding Cas9, an sgRNA that targets SEQ ID NO: 3, and an sgRNA that targets SEQ ID NO: 6 into an embryo of a mouse, thereby causing a disruption in the embryo's endogenous CD132 gene;
culturing the embryo; and
transplanting the embryo to a recipient mouse to produce the genetically-modified mouse.
3. The method of claim 2 , wherein the embryo has NOD/scid mutation.
4. The method of claim 3 , wherein the method further comprises establishing a stable mouse line from progenies of the genetically-modified mouse.
5. A genetically-modified mouse obtained from progenies of the genetically-modified mouse produced by the method of claim 2 .
6. The mouse of claim 1 , wherein the mouse is homozygous with respect to the disruption.
7. The mouse of claim 1 , wherein the mouse is heterozygous with respect to the disruption.