EXTRACELLULAR MATRIX IN MICE LACKING THROMBOSPONDIN 2

描述：(摘自应用程序)：凝血酶敏感蛋白2(TSP2)是一种 胞外蛋白，其功能复杂且知之甚少。 两个缺乏TSP2的小鼠已经由同源的 胚胎干细胞中的重组。这些小鼠表现出广泛的光谱 结缔组织和细胞异常，包括脆弱的皮肤， 皮肤和肌腱异常纤维，皮肤成纤维细胞粘连 缺陷，肌腱和韧带松弛，骨密度增加。老鼠 也有血管密度显著增加和出血倾向， 这些发现可能也有细胞外基质的基础。 拟议的工作将集中在：1)胶粘剂缺陷的性质 成纤维细胞；基质和细胞表面的贡献 将检查ECM蛋白的受体；(2)细胞外基质的分子基础 皮肤的脆性增加和异常胶原的存在 结缔组织中的纤维；方法将包括免疫荧光 分析和传输、扫描和免疫金电子显微镜；3) TSP-NICE患者骨密度升高的潜在原因； 将评估骨吸收和合成方面可能存在的缺陷；4) 出血素质；TSP2在稳定脑出血系绳系带中的作用 对内皮下层的血小板进行检查；5)伤口研究 愈合和皮下海绵植入物。因此，这项工作可能会 对基质合成和组装的研究具有重要意义， 骨骼生长和动态平衡。此外，对其作用的阐明 TSP2在这些不同的过程中很可能揭示出以前没有被怀疑的 结缔组织中TSP2及相关蛋白的功能。

DESCRIPTION: (taken from the application): Thrombospondin 2 (TSP2) is an extracellular protein whose functions are complex and poorly understood. Two lines of mice that lack TSP2 have been generated by homologous recombination in embryonic stem cells. These mice display a wide spectrum of connective tissue and cellular abnormalities, including fragile skin, abnormal fibrils in skin and tendon, skin fibroblasts with adhesive defects, lax tendons and ligaments and increased bone density. The mice also have a marked increase in vascular density and a bleeding tendency, findings which might also have a basis in the extracellular matrix. The proposed work will focus on: 1) the nature of the adhesive defects in fibroblasts; the contributions of the substratum and of cell-surface receptors from ECM proteins will be examined; (2) the molecular basis for the increased fragility of skin and the presence of abnormal collagen fibrils in connective tissues; approaches will include immunofluorescence analyses and transmission, scanning and immunogold electron microscopy; 3) the underlying cause for the increased bone density in TSP-null nice; possible defects in bone resorption and synthesis will be assessed; 4) the bleeding diathesis; a role for TSP2 in stabilizing the tethering of platelets to the sub-endothelium will be examined; 5) studies of wound healing and subcutaneous sponge implants. This work may therefore have significant implications for studies of matrix synthesis and assembly, bone growth, and homeostasis. Moreover, the elucidation of the role of TSP2 in these diverse processes is likely to reveal previously unsuspected functions for TSP2 and related proteins in connective tissue.