Neurologic defects and selective disruption of basement membranes in mice lacking entactin-1/nidogen-1
Neurologic defects and selective disruption of basement membranes in mice lacking entactin-1/nidogen-1
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DOI：
10.1097/01.lab.0000042240.52093.0f
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发表时间：
2002-12-01
影响因子：
5
通讯作者：
Chung, AE
中科院分区：
文献类型：
--
作者：
Dong, LJ;Chen, Y;Chung, AE
巢蛋白-1（nidogen-1）是基底膜的普遍存在的组分。根据体外实验，entactin-1被认为在维持基底膜结构完整性方面发挥作用，因为它与其他成分（例如IV型胶原蛋白和层粘连蛋白）具有结合亲和力。内分泌蛋白-1还与细胞表面上的整联蛋白受体相互作用以介导细胞粘附、铺展和运动。在本研究中提出的小鼠中的entactin-1基因的靶向破坏揭示了entacin-1位点的重复。功能位点的纯合突变体缺乏entactin-1 mRNA和蛋白质，并且经常表现出类似于痉挛的症状和后腿肌肉控制的丧失。这些行为模式表明中枢神经系统存在神经缺陷，从而提供了将entactin-1与神经肌肉系统的正常功能联系起来的遗传证据。在纯合突变体中，基底膜的结构改变仅在选定的位置发现，包括脑毛细血管和透镜囊。表面检查的其他组织中的基底膜形态似乎正常。这些观察结果表明，entactin-1的功能丧失导致高度组织特异性的病理变化。
Entactin-1 (nidogen-1) is an ubiquitous component of basement membranes. From in vitro experiments, entactin-1 was assigned a role in maintaining the structural integrity of the basement membrane because of its binding affinity to other components, such as type IV collagen and laminin. Entactin-1 also interacts with integrin receptors on the cell surface to mediate cell adhesion, spreading, and motility. Targeted disruption of the entactin-1 gene in the mouse presented in this study revealed a duplication of the entacin-1 locus. Homozygous mutants for the functional locus lacked entactin-1 mRNA and protein and often displayed seizure-like symptoms and loss of muscle control in the hind legs. The behavior patterns suggested the presence of neurologic deficits in the central nervous system, thus providing genetic evidence linking entactin-1 to proper functions of the neuromuscular system. In homozygous mutants, structural alterations in the basement membranes were found only in selected locations including brain capillaries and the lens capsule. The morphology of the basement membranes in other tissues examined superficially appeared to be normal. These observations suggest that the lost functions of entactin-1 result in pathologic changes that are highly tissue specific.