Morrow M A, Mayer E W, Perez C A, Adlam M, Siu G
Department of Biology, State University of New York, New Paltz 12561-2499, USA.
Mol Immunol. 1999 Jun;36(8):491-503. doi: 10.1016/s0161-5890(99)00071-1.
The Id proteins are inhibitors of basic-Helix-Loop-Helix transcription factor function that have been implicated in the control of cell differentiation and proliferation. To study the role of Id proteins in the control of T cell development, we generated transgenic mice that overexpress the Id2 protein in thymocytes. We detect a significant expansion of the early CD4(-)CD8(+)TCR(-) thymocyte stage and a depletion of the thymocytes of the subsequent developmental stages. These data indicate that the overexpression of Id2 leads to a stage-specific developmental block early in thymopoiesis. In addition, progeny mice from five of the six Id2 transgenic founder lines succumb to aggressive T cell hyperproliferation that resembles lymphoma. Thus, overexpression of the Id2 protein has profound effects on T cell development and oncogenesis, consistent with the hypothesis that the bHLH proteins play critical roles in these processes.
Id蛋白是碱性螺旋-环-螺旋转录因子功能的抑制剂,与细胞分化和增殖的调控有关。为了研究Id蛋白在T细胞发育调控中的作用,我们构建了在胸腺细胞中过表达Id2蛋白的转基因小鼠。我们检测到早期CD4(-)CD8(+)TCR(-)胸腺细胞阶段显著扩增,以及随后发育阶段胸腺细胞的减少。这些数据表明,Id2的过表达导致胸腺生成早期阶段特异性的发育阻滞。此外,六个Id2转基因奠基系中的五个的子代小鼠死于类似于淋巴瘤的侵袭性T细胞过度增殖。因此,Id2蛋白的过表达对T细胞发育和肿瘤发生有深远影响,这与bHLH蛋白在这些过程中起关键作用的假设一致。