EXTRACELLULAR MATRIX IN MICE LACKING THROMBOSPONDIN 2

描述：（摘自应用程序）：血小板反应蛋白2（TSP 2）是一种 功能复杂且知之甚少的细胞外蛋白质。 已经通过同源重组产生了两种缺乏TSP 2的小鼠品系。 胚胎干细胞中的基因重组这些老鼠表现出广泛的 结缔组织和细胞异常，包括脆弱的皮肤， 皮肤和肌腱中的异常原纤维，皮肤成纤维细胞与粘合剂 缺陷、松弛的肌腱和韧带以及增加的骨密度。小鼠 也有血管密度显著增加和出血倾向， 这些发现也可能与细胞外基质有关。 建议的工作将集中在：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）ECM蛋白的分子基础 皮肤脆弱性增加和胶原蛋白异常 结缔组织中的纤维;方法将包括免疫荧光 分析和透射、扫描和免疫金电子显微镜; 3） TSP阴性大鼠骨密度增加的根本原因; 评估骨吸收和合成中可能存在的缺陷; 4） 出血素质; TSP 2在稳定 将检查血小板到内皮下的情况; 5）伤口研究 愈合和皮下海绵植入物。因此，这项工作可能 对基质合成和组装的研究具有重要意义， 骨骼生长和体内平衡此外，阐明的作用 TSP 2在这些不同的过程中可能揭示了以前未被怀疑的 TSP 2和相关蛋白在结缔组织中的功能。

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.