EXTRACELLULAR MATRIX IN MICE LACKING THROMBOSPONDIN 2

缺乏血小板反应蛋白 2 的小鼠的细胞外基质

• 批准号: 2681754
• 负责人: PAUL BORNSTEIN
• 金额: $ 25.59万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-07-15 至 2002-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2681754
• 关键词: bone density; cell adhesion; collagen; extracellular matrix; extracellular matrix proteins; fibroblasts; gene deletion mutation; gene targeting; genetically modified animals; immunoelectron microscopy; laboratory mouse; molecular pathology; receptor expression; scanning electron microscopy; thrombospondins; transmission electron microscopy

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.

描述：（摘自申请）：血小板反应蛋白 2 (TSP2) 是一种 细胞外蛋白，其功能复杂且知之甚少。 通过同源基因产生了两个缺乏 TSP2 的小鼠品系 胚胎干细胞中的重组。这些小鼠表现出广泛的谱系 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、具有粘合剂的皮肤成纤维细胞 缺损、肌腱和韧带松弛以及骨密度增加。老鼠们 血管密度也明显增加，有出血倾向， 这些发现可能也有细胞外基质的基础。 拟议的工作将重点关注：1）粘合剂缺陷的性质 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)分子基础 皮肤脆弱性增加和异常胶原蛋白的存在 结缔组织中的原纤维；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 无效的尼斯骨密度增加的根本原因； 将评估骨吸收和合成中可能存在的缺陷； 4） 出血素质； TSP2 在稳定束缚中的作用 将检查内皮下的血小板； 5) 伤口研究 愈合和皮下海绵植入物。因此，这项工作可能具有 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，阐明了 TSP2 在这些不同的过程中可能会揭示以前未曾怀疑过的信息 TSP2 和结缔组织中相关蛋白的功能。