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Publication : Differences between immunodeficient mice generated by classical gene targeting and CRISPR/Cas9-mediated gene knockout.

First Author  Lee JH Year  2018
Journal  Transgenic Res Volume  27
Issue  3 Pages  241-251
PubMed ID  29594927 Mgi Jnum  J:265348
Mgi Id  MGI:6199341 Doi  10.1007/s11248-018-0069-y
Citation  Lee JH, et al. (2018) Differences between immunodeficient mice generated by classical gene targeting and CRISPR/Cas9-mediated gene knockout. Transgenic Res 27(3):241-251
abstractText  Immunodeficient mice are widely used for pre-clinical studies to understand various human diseases. Here, we report the generation of four immunodeficient mouse models using CRISPR/Cas9 system without inserting any foreign gene sequences such as Neo(R) cassettes and their characterization. By eliminating any possible effects of adding a Neo(R) cassette, our mouse models may allow us to better elucidate the in vivo functions of each gene. Our FVB-Rag2(-/-), B6-Rag2(-/-), and BALB/c-Prkdc(-/-) mice showed phenotypes similar to those of the earlier immunodeficient mouse models, including a lack of mature B cells and T cells and an increase in the number of CD45(+)DX-5(+) natural killer cells. However, B6-Il2rg(-/-) mice had a unique phenotype, with a lack of mature B cells, increased number of T cells, and decreased number of natural killer cells. Additionally, serum immunoglobulin levels in all four immunodeficient mouse models were significantly reduced when compared to those in wild-type mice with the exception of IgM in B6-Il2rg(-/-) mice. These results indicate that our immunodeficient mouse models are a robust tool for in vivo studies of the immune system and will provide new insights into the variation in phenotypic outcomes resulting from different gene-targeting methodologies.
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