TYPE V COLLAGEN AND CORNEAL STROMA

描述：角膜的基质成分对角膜的生长至关重要。 在视觉通路中起到透明屏障的作用。 除了 I型胶原蛋白，主要的角膜胶原蛋白，高达20%， 角膜的胶原由胶原V组成，胶原V是角膜中的次要成分。 其他组织。 该项目测试了V型胶原蛋白 调节角膜组织，特别是， 异型胶原I/V原纤维。 它采用pN/pN鼠标， 胶原蛋白a2（V）中的靶向突变。 既往结果显示异常 在纯合子和杂合子突变体中角膜基质的发育是 与这一假设相一致。 具体目标是检验假设的以下预测： 1. 角膜胶原纤维的直径取决于内含物或 排除角膜异型纤维中的V型胶原。 2. 一 胶原蛋白V的突变改变了其通过合成和 分泌途径 3. 胶原V和胶原I/V异型原纤维结合 以配体特异性方式与角膜细胞表面受体结合。 4. 突变的V型胶原改变了角膜的功能完整性 基质。 拟议的实验将提供有关 细胞/基质相互作用的细胞机制和关于V型的作用 胶原蛋白在角膜基质的发展和重塑，如发生 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.