Fernández-Llebrez P, Grondona J M, Pérez J, López-Aranda M F, Estivill-Torrús G, Llebrez-Zayas P F, Soriano E, Ramos C, Lallemand Y, Bach A, Robert B
Departamento de Biología Celular, Genética y Fisiología, Facultad de Ciencias, Universidad de Málaga, Málaga, Spain.
J Neuropathol Exp Neurol. 2004 Jun;63(6):574-86. doi: 10.1093/jnen/63.6.574.
Msx1 is a regulatory gene involved in epithelio-mesenchymal interactions in limb formation and organogenesis. In the embryonic CNS, the Msx1 gene is expressed along the dorsal midline. Msx1 mutant mice have been obtained by insertion of the nlacZ gene in the Msx1 homeodomain. The most important features of homozygous mutants that we observed were the absence or malformation of the posterior commissure (PC) and of the subcommissural organ (SCO), the collapse of the cerebral aqueduct, and the development of hydrocephalus. Heterozygous mutants developed abnormal PC and reduced SCO, as revealed by specific antibodies against SCO secretory glycoproteins. About one third of the heterozygous mutants also showed hydrocephalus. Other defects displayed by homozygous mutants were ependymal denudation, subventricular cavitations and edema, and underdevelopment of the pineal gland and subfornical organ. Some homozygous mutants developed both SCO and PC, probably as a consequence of genetic redundancy with Msx2. However, these mutants did not show SCO-immunoreactive glycoproteins and displayed obstructive hydrocephalus. This suggests that Msx1 is necessary for the synthesis of SCO glycoproteins, which would then be required for the maintenance of an open aqueduct.
Msx1是一种调控基因，参与肢体形成和器官发生过程中的上皮-间充质相互作用。在胚胎中枢神经系统中，Msx1基因沿背中线表达。通过将nlacZ基因插入Msx1同源结构域获得了Msx1突变小鼠。我们观察到的纯合突变体的最重要特征是后连合（PC）和连合下器官（SCO）缺失或畸形、中脑导水管塌陷以及脑积水的发生。通过针对SCO分泌糖蛋白的特异性抗体发现，杂合突变体出现PC异常和SCO减少。约三分之一的杂合突变体也表现出脑积水。纯合突变体显示的其他缺陷包括室管膜剥脱、脑室下空洞形成和水肿，以及松果体和穹窿下器官发育不全。一些纯合突变体同时发育出SCO和PC，这可能是与Msx2基因冗余的结果。然而，这些突变体未显示SCO免疫反应性糖蛋白，并表现出梗阻性脑积水。这表明Msx1对于SCO糖蛋白的合成是必需的，而SCO糖蛋白对于维持导水管通畅是必需的。
