Ohno H, Aoe T, Taki S, Kitamura D, Ishida Y, Rajewsky K, Saito T
Division of Molecular Genetics, Chiba University, School of Medicine, Japan.
EMBO J. 1993 Nov;12(11):4357-66. doi: 10.1002/j.1460-2075.1993.tb06120.x.
CD3 zeta is a component of the T cell antigen receptor (TCR) complex and is important for signal transduction. We have established mice selectively lacking CD3 zeta but able to express CD3 eta, a polypeptide produced from the same locus through alternative splicing, using the method of gene targeting in embryonic stem cells. In homozygous mutant mice, the numbers of thymocytes and peripheral T cells were greatly reduced and the expression levels of TCR on these cells were 5-fold lower than those on wild-type cells. By contrast, TCR gamma delta+ intestinal intraepithelial lymphocytes were not obviously affected by the mutation. T cells from homozygous mutants exhibited an impaired proliferative response. These results imply that CD3 zeta has a critical role in the development and signal transduction of T cells in vivo.
CD3ζ是T细胞抗原受体（TCR）复合物的一个组成部分，对信号转导很重要。我们利用胚胎干细胞基因打靶方法，建立了选择性缺失CD3ζ但能够表达CD3η的小鼠，CD3η是通过可变剪接从同一基因座产生的一种多肽。在纯合突变小鼠中，胸腺细胞和外周T细胞数量大幅减少，这些细胞上TCR的表达水平比野生型细胞低5倍。相比之下，TCRγδ+肠上皮内淋巴细胞并未受到该突变的明显影响。纯合突变体的T细胞表现出增殖反应受损。这些结果表明，CD3ζ在体内T细胞的发育和信号转导中起关键作用。
