Department of Pediatrics, McGill University, Montréal, Québec, Canada.
Clin Genet. 2010 Apr;77(4):314-25. doi: 10.1111/j.1399-0004.2010.01397.x.
Claudins are the structural and molecular building blocks of tight junctions. Individual cells express more than one claudin family member, which suggests that a combinatorial claudin code that imparts flexibility and dynamic regulation of tight junction function could exist. Although we have learned much from manipulating claudin expression and function in cell lines, loss-of-function and gain-of-function experiments in animal model systems are essential for understanding how claudin-based boundaries function in the context of a living embryo and/or tissue. These in vivo manipulations have pointed to roles for claudins in maintaining the epithelial integrity of cell layers, establishing micro-environments and contributing to the overall shape of an embryo or tissue. In addition, loss-of-function mutations in combination with the characterization of mutations in human disease have demonstrated the importance of claudins in regulating paracellular transport of solutes and water during normal physiological states. In this review, we will discuss specific examples of in vivo studies that illustrate the function of claudin family members during development and in disease.
紧密连接的结构和分子基础是 Claudin 蛋白。每个细胞表达多种 Claudin 家族成员，这表明可能存在一种组合 Claudin 密码，赋予紧密连接功能的灵活性和动态调节。虽然我们已经从操纵细胞系中的 Claudin 表达和功能中学到了很多，但在动物模型系统中进行功能丧失和功能获得实验对于理解 Claudin 为基础的边界在活胚胎和/或组织中的功能至关重要。这些体内操作表明 Claudin 在维持细胞层的上皮完整性、建立微环境以及影响胚胎或组织的整体形状方面发挥作用。此外，功能丧失突变与人类疾病中突变的特征相结合，证明了 Claudin 在调节正常生理状态下溶质和水的旁细胞转运中的重要性。在这篇综述中，我们将讨论一些体内研究的具体实例，这些实例说明了 Claudin 家族成员在发育和疾病中的功能。
