TYPE V COLLAGEN AND CORNEAL STROMA

描述：角膜基质的组成对其 在视觉通路中起到透明屏障的作用。除了……之外 I型胶原是主要的角膜胶原蛋白，高达20%的 角膜的胶原蛋白是由胶原蛋白V组成的，这是一种次要成分 其他纸巾。这个项目测试了V型胶原蛋白的假说 调节角膜组织，特别是角膜的组装和直径 异型胶原I/V纤维。它采用PN/PN鼠标，携带 A2(V)胶原蛋白的靶向突变。先前的检查结果显示异常 纯合子和杂合子突变体的角膜基质发育 与这一假设一致。 具体目的是检验该假说的以下预测： 1.角膜胶原纤维的直径取决于包裹物或 在异型角膜纤维中排除V型胶原。2.A V型胶原的突变改变了它通过合成和 分泌途径。3.V型胶原和I/V型胶原异型纤维结合 以配体特有的方式与角质细胞表面受体结合。4. V型胶原突变改变角膜的功能完整性 斯特尔玛。 拟议的实验将提供关于 细胞/基质相互作用的细胞机制及关于V型的作用 胶原蛋白在角膜基质发育和重塑等方面的发生 在伤口愈合过程中。

DESCRIPTION: The matrix composition of the cornea is critical to its function as a transparent barrier in the visual pathway. In addition to collagen type I, the major corneal collagen, up to 20 percent of the collagen of the cornea is composed of collage V, a minor constituent in other tissues. This project tests the hypothesis that type V collagen regulates corneal organization, specifically, the assembly and diameter of heterotypic collagen I/V fibrils. It employs the pN/pN mouse which carries a targeted mutation in collagen a2(V). Previous esults showing abnormal corneal stroma development in both homozygote and heterozygote mutants are consistent with this hypothesis. The Specific Aims are to test the following predictions of the hypothesis: 1. The diameter of corneal collagen fibrils depends upon the inclusion or exclusion of type V collagen in heterotypic fibrils of the cornea. 2. A mutation of collagen V alters its transit through the synthetic and secretory pathway. 3. Collagen V and Collagen I/V heterotype fibrils bind to keratocyte cell surface receptors in ligand specific fashions. 4. Mutant type V collagen alters the functional integrity of the corneal stroma. The proposed experiments will provide fundamental information about the cellular mechanisms of cell/matrix interaction and about the role of type V collagen in corneal stroma development and in remodeling such as occurs during wound healing.