A point mutation in the extracellular domain of CD4 completely abolishes CD4 T cell development in C57BL/6 mouse

Publication date: December 2017
Source:Molecular Immunology, Volume 92
Author(s): Huijie Wang, Saichao Li, Tianzhu Chao, Xugang Wang, Lijin Shi, Lichen Zhang, Yinming Liang, Qianqian Zheng, Liaoxun Lu
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^I99N 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.



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