CRISPR/Cas9-Mediated Deletion of Foxn1 in NOD/SCID/ IL2rg−/− Mice Results in Severe Immunodeficiency

CRISPR/Cas9-Mediated Deletion of Foxn1 in NOD/SCID/ IL2rg−/− Mice Results in Severe Immunodeficiency

Abstract

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 from NOD/SCID/IL2rg-/- (NSI) mice using the CRISPR/Cas9 system. The NSIN mice were deficient in B, T, and NK cells and not only showed impaired T cell reconstitution and thymus regeneration after allogeneic bone marrow nucleated cell transplantation but also exhibited improved capacity to graft both leukemic and solid tumor cells compared with NSI, NOG, and NDG mice. Moreover, the 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.

Authors: Wei X1,2,3, Lai Y2,3, Li B2,3, Qin L2,3, Xu Y1,2,3, Lin S2,3, Wang S2,3, Wu Q2,3, Liang Q4, Huang G5, Deng Q5, Liu P6, Wu D2,3, Lai L2,3, Yao Y7,8, Li P9,10.

Influence Factor: 4.0738

Citation: Scientific Reports 7, 7720 (2017).

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