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

Jae Hoon Lee, Jong Hyung Park, Tae Wook Nam, Sun Min Seo, Jun Young Kim, Han Kyul Lee, Jong Hyun Han, Song Yi Park, Yang Kyu Choi, Han Woong Lee

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

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 NeoR cassettes and their characterization. By eliminating any possible effects of adding a NeoR 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.

Original languageEnglish
Pages (from-to)241-251
Number of pages11
JournalTransgenic Research
Volume27
Issue number3
DOIs
Publication statusPublished - 2018 Jun 1

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Animal Science and Zoology
  • Agronomy and Crop Science
  • Genetics

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    Lee, J. H., Park, J. H., Nam, T. W., Seo, S. M., Kim, J. Y., Lee, H. K., Han, J. H., Park, S. Y., Choi, Y. K., & Lee, H. W. (2018). Differences between immunodeficient mice generated by classical gene targeting and CRISPR/Cas9-mediated gene knockout. Transgenic Research, 27(3), 241-251. https://doi.org/10.1007/s11248-018-0069-y