Generation of a new strain of NOD/SCID/IL2Rγ mice with targeted disruption of Prkdc and IL2Rγ genes using CRISPR/Cas9 system / 南方医科大学学报

ABSTRACT

<p><b>OBJECTIVE</b>The NOD/SCID/IL2Rγ (NSG) mouse strain is the most widely used immunodeficient strain for xenograft transplantation. However, the existing SCID mutation is a spontaneous mutation of the Prkdc gene, which leads to leaky T cell developmental block and difficulty in genotyping. It is therefore important to develop a new strain of NSG mice with targeted disruption of Prkdc and IL2Rγ genes.</p><p><b>METHODS</b>Targeted disruption of Prkdc and IL2Rγ genes was achieved using the CRISPR/Cas9 system. By intercrossing the knockout and NOD mice, we obtained a novel strain of NOD/SCID/IL2Rγ(NSG) mice, denoted as cNSG (Chinese NSG) mice.</p><p><b>RESULTS</b>In addition to the NOD mutation, cNSG mice exhibited a complete absence of T cells, B cells and NK cells. cNSG mice allowed more efficient engraftment of human cancer cells than the commonly used immunodeficient nude mice.</p><p><b>CONCLUSION</b>cNSG mice will provide an important xenotransplantation model for biomedical research.</p>