Dataset Information

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.

SUBMITTER: Wei X

PROVIDER: S-EPMC5552779 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Publications

CRISPR/Cas9-Mediated Deletion of Foxn1 in NOD/SCID/IL2rg<sup>-/-</sup> Mice Results in Severe Immunodeficiency.

Wei Xinru X Lai Yunxin Y Li Baiheng B Qin Le L Xu Youdi Y Lin Simiao S Wang Suna S Wu Qiting Q Liang Qiubin Q Huang Guohua G Deng Qiuhua Q Liu Pentao P Wu Donghai D Lai Liangxue L Yao Yao Y Li Peng P

Scientific reports 20170810 1

Immunodeficient mice engrafted with either normal or cancerous human cells are widely used in basic and translational research. In particular, NOD/SCID/IL2rg<sup>-/-</sup> 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 multipl ...[more]

PMID: 28798321

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Project description:Immunodeficient animals are valuable models for the engraftment of exogenous tissues; they are widely used in many fields, including the creation of humanized animal models, as well as regenerative medicine and oncology. Compared with mice, laboratory rats have a larger body size and can more easily undergo transplantation of various tissues and organs. Considering the absence of high-quality resources of immunodeficient rats, we used the CRISPR/Cas9 genome editing system to knock out the interleukin-2 receptor gamma chain gene (Il2rg) in F344/Jcl rats-alone or together with recombination activating gene 2 (Rag2)-to create a high-quality bioresource that researchers can freely use: severe combined immunodeficiency (SCID) rats. We selected one founder rat with frame-shift mutations in both Il2rg (5-bp del) and Rag2 ([1-bp del+2-bp ins]/[7-bp del+2-bp ins]), then conducted mating to establish a line of immunodeficient rats. The immunodeficiency phenotype was preliminarily confirmed by the presence of severe thymic hypoplasia in Il2rg-single knockout (sKO) and Il2rg/Rag2-double knockout (dKO) rats. Assessment of blood cell counts in peripheral blood showed that the white blood cell count was significantly decreased in sKO and dKO rats, while the red blood cell count was unaffected. The decrease in white blood cell count was mainly caused by a decrease in lymphocytes. Furthermore, analyses of lymphocyte populations via flow cytometry showed that the numbers of B cells (CD3- CD45+) and natural killer cells (CD3- CD161+) were markedly reduced in both knockout rats. In contrast, T cells were markedly reduced but showed slightly different results between sKO and dKO rats. Notably, our immunodeficient rats do not exhibit growth retardation or gametogenesis defects. This high-quality SCID rat resource is now managed by the National BioResource Project in Japan. Our SCID rat model has been used in various research fields, demonstrating its importance as a bioresource.

Dataset Information

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

Publications

CRISPR/Cas9-Mediated Deletion of Foxn1 in NOD/SCID/IL2rg<sup>-/-</sup> Mice Results in Severe Immunodeficiency.

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Dataset Information

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

Publications

CRISPR/Cas9-Mediated Deletion of Foxn1 in NOD/SCID/IL2rg<sup>-/-</sup> Mice Results in Severe Immunodeficiency.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

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