CRISPRCas9-Mediated Deletionof Foxn1 in NODSCIDIL2rg−− Mice Results in Severe Immunodeficiency

Immunodeficient mice engrafted with either normal or cancerous human cells are widely used in basic and translational research. In particular, NOD/SCID/IL2rg−/− mice can support the growth of various types of human cancer cells. However, the hairs of these mice interfere with the observation and imaging of engrafted tissues. Therefore, novel hairless strains exhibiting comparable immunodeficiency would be beneficial. Recently, the CRISPR/Cas9 system has been used for efficient multiplexed genome editing. In the present study, we generated a novel strain of nude NOD/SCID/IL2rg−/− (NSIN) mice by knocking out Foxn1 using the CRISPR/Cas9 system from NOD/SCID/IL2rg−/− (NSI) mice. NSIN mice were deficient in B, T, and NK cells, which showed impaired T cell reconstitution and thymus regeneration after allogeneic bone marrow nucleated cell transplantation, and exhibited improved capacities of grafting both leukemic and solid tumor cells compared with NSI, NOG and NDG mice. Moreover, NSIN mice facilitated the monitoring and in vivo imaging of both leukemia and solid tumors. Therefore, our NSIN mice provide a new platform for xenograft mouse models in basic and translational research.