Geisert Eldon E, Williams Robert W, Geisert Grace R, Fan Liying, Asbury Andrew M, Maecker Holden T, Deng Jun, Levy Shoshana
Department of Anatomy and Neurobiology, and Neuroscience Institute, University of Tennessee, Health Science Center, Memphis, Tennessee 38163, USA.
J Comp Neurol. 2002 Nov 4;453(1):22-32. doi: 10.1002/cne.10364.
A key issue in the development of the central nervous system (CNS) is understanding the molecular mechanisms regulating cell number. The present study examines the role of CD81 (previously known as TAPA, the target of the antiproliferative antibody) in the control of brain size and glial cell number. CD81 is a member of the tetraspanin family of proteins. This group of small membrane proteins is associated with the regulation of cell migration and mitotic activity. Glial cells express CD81, and antibodies directed against this protein suppress the mitotic activity of cultured cells. In this study, we examine the effects of the CD81 -/- mutation on the CNS of mature mice. These mice have extremely large brains, as much as 30% larger than the brains of wild-type (+/+) littermates. The increase in brain weight is accompanied by an increase in the number astrocytes and microglia, whereas the number of neurons and oligodendrocytes in the CD81 -/- animals appears to be normal. When the CD81 -/- mutation is placed on different genetic backgrounds, there is a remarkable range in the penetrance of the null allele phenotype, demonstrating that the mutation can be affected by modifier loci. This work provides support for the role of CD81 in the regulation of astrocyte and microglial number, perhaps by regulating cell proliferation by a contact inhibition-dependent mechanism.
中枢神经系统（CNS）发育中的一个关键问题是了解调节细胞数量的分子机制。本研究探讨了CD81（以前称为TAPA，抗增殖抗体的靶点）在控制脑大小和神经胶质细胞数量方面的作用。CD81是四跨膜蛋白家族的成员。这组小的膜蛋白与细胞迁移和有丝分裂活性的调节有关。神经胶质细胞表达CD81，针对该蛋白的抗体可抑制培养细胞的有丝分裂活性。在本研究中，我们研究了CD81基因敲除突变对成熟小鼠中枢神经系统的影响。这些小鼠的大脑极大，比野生型（+/+）同窝小鼠的大脑大30%。脑重量的增加伴随着星形胶质细胞和小胶质细胞数量的增加，而CD81基因敲除动物中的神经元和少突胶质细胞数量似乎正常。当将CD81基因敲除突变置于不同的遗传背景下时，无效等位基因表型的外显率有显著差异，表明该突变可受修饰基因座的影响。这项工作为CD81在调节星形胶质细胞和小胶质细胞数量方面的作用提供了支持，可能是通过依赖接触抑制的机制调节细胞增殖来实现的。
