Wang Huijie, Li Saichao, Chao Tianzhu, Wang Xugang, Shi Lijin, Zhang Lichen, Liang Yinming, Zheng Qianqian, Lu Liaoxun
Laboratory of Genetic Regulators in the Immune System, School of Laboratory Medicine, Xinxiang Medical University, Henan Province 453003, China; Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, Xinxiang Medical University, Xinxiang, Henan, China; Xinxiang Assegai Medical Laboratory Institute, Xinxiang, Henan, China.
Laboratory of Mouse Genetics, Institute of Psychiatry and Neuroscience, Xinxiang Medical University, Henan Province 453003, China.
Mol Immunol. 2017 Dec;92:12-20. doi: 10.1016/j.molimm.2017.09.015. Epub 2017 Oct 10.
In this study, we performed ENU mutagenesis and multi-parameter flow cytometric analysis in C57BL/6 mice to uncover novel genes or alleles regulating immune cell development. We identified a novel mutant allele of Cd4 gene which completely blocked development of a major subset of T cells named CD4 T cell. Our data for the first time showed experimentally in mice the critical role of the first extracellular domain, by obtaining mice with a loss of function mutation from Ile to Asn at the position 99 of CD4 (I99N). Interestingly, such CD4 mutant protein can be expressed on the surface of human cells, and the mRNA stability could be also affected by this point mutation, suggesting that absence of CD4 T cells in mice rooted in the deficiency in function and expression of CD4. In addition, we used this novel CD4 T cell deficient model as recipient mice for adoptive transfer experiment, and showed that it could be an optimal model for study of CD4 T cells.
