TYPE VIII COLLAGEN AND EXTRACELLULAR MATRIX

拟议的研究项目是一个更大的研究组合的一部分 项目的长期目标是了解其功能和 胶原蛋白在特定组织中的组装。假设是 细胞外基质的特殊微结构 不同的组织由组织依赖的表达决定 拟议的项目集中在转录和蛋白质变体上 重点揭示型胶原蛋白的功能意义 在血管和心肌的壁中，它是已知的 被表达出来。不同突变的VIII型胶原基因结构 将被制造并引入胚胎干细胞，以便能够 获得嵌合小鼠。显性阴性突变体和基因敲除突变体都会 被制作出来。对这些小鼠组织的研究应该会成功 可以看到并更好地理解缺陷类型的后果 胶原蛋白。这将使识别疾病成为可能 胶原蛋白基因突变导致的人类表型。 最终，表型相似的患者的血液样本将 收集并筛查VIII型胶原基因突变。

The proposed research project is part of a larger combination of research projects the long-term goal of which is to understand the function and assembly of collagenous proteins in specific tissues. the hypothesis is that the specific microarchitecture o the extra-cellular matrix in different tissues is determined by the tissue dependent expression of transcript and protein variants The proposed project concentrates on revealing the functional significance of type VIII collagen especially in the walls of blood vessel and the heart muscle, in which it is known to be expressed. Different mutated type VIII collagen gene constructs will be made and introduced into embryonic stem cells to be able to obtain chimeric mice. Both dominant-negative and knock-out mutants will be produced. Studies on the tissues of these mice should make it possible to see and better understand the consequences of defective type VIII collagen. This would enable the identification of disease phenotypes in humans caused by mutations in the type VIII collagen genes. Ultimately blood samples from patients with resembling phenotypes would be collected and screened for type VIII collagen gene mutations.