Verbeek S, Izon D, Hofhuis F, Robanus-Maandag E, te Riele H, van de Wetering M, Oosterwegel M, Wilson A, MacDonald H R, Clevers H
Department of Immunology, University Hospital, Utrecht, The Netherlands.
Nature. 1995 Mar 2;374(6517):70-4. doi: 10.1038/374070a0.
Two candidate genes for controlling thymocyte differentiation, T-cell factor-1 (Tcf-1) and lymphoid enhancer-binding factor (Lef-1), encode closely related DNA-binding HMG-box proteins. Their expression pattern is complex and largely overlapping during embryogenesis, yet restricted to lymphocytes postnatally. Here we generate two independent germline mutations in Tcf-1 and find that thymocyte development in (otherwise normal) mutant mice is blocked at the transition from the CD8+, immature single-positive to the CD4+/CD8+ double-positive stage. In contrast to wild-type mice, most of the immature single-positive cells in the mutants are not in the cell cycle and the number of immunocompetent T cells in peripheral lymphoid organs is reduced. We conclude that Tcf-1 controls an essential step in thymocyte differentiation.
两个控制胸腺细胞分化的候选基因，即T细胞因子-1（Tcf-1）和淋巴样增强子结合因子（Lef-1），编码密切相关的DNA结合HMG盒蛋白。它们的表达模式复杂，在胚胎发育过程中大部分重叠，但出生后仅限于淋巴细胞。在这里，我们在Tcf-1中产生了两个独立的种系突变，发现在（其他方面正常的）突变小鼠中，胸腺细胞发育在从CD8 +未成熟单阳性向CD4 + / CD8 +双阳性阶段的转变过程中受阻。与野生型小鼠相比，突变体中大多数未成熟单阳性细胞不在细胞周期中，外周淋巴器官中具有免疫活性的T细胞数量减少。我们得出结论，Tcf-1控制胸腺细胞分化中的一个关键步骤。
