TYPE VIII COLLAGEN AND EXTRACELLULAR MATRIX

VIII 型胶原蛋白和细胞外基质

• 批准号: 2293165
• 负责人: MIIKKA S. VIKKULA
• 金额: $ 2.86万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-09-30 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2293165
• 关键词: TYPE; VIII; COLLAGEN; EXTRACELLULAR; MATRIX

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.

拟议的研究项目是更大的研究组合的一部分 项目的长期目标是了解功能和 胶原蛋白在特定组织中的组装。 假设是 细胞外基质的特定微结构 不同的组织是由组织依赖性表达决定的 转录本和蛋白质变体拟议的项目集中于 特别揭示了 VIII 型胶原蛋白的功能意义 在血管壁和心肌中，已知 来表达。 不同的突变 VIII 型胶原蛋白基因构建体 将被制造并引入胚胎干细胞，以便能够 获得嵌合小鼠。显性失活突变体和敲除突变体都会 被生产出来。 对这些小鼠组织的研究应该能够 可以看到并更好地理解缺陷类型的后果 VIII 胶原蛋白。 这将有助于识别疾病 由 VIII 型胶原蛋白基因突变引起的人类表型。 最终，来自具有相似表型的患者的血液样本将 收集并筛选 VIII 型胶原蛋白基因突变。