Fibromodulin-null mice have abnormal collagen fibrils, tissue organization, and altered lumican deposition in tendon

作     者：Svensson, L Aszódi, A Reinholt, FP Fässler, R Heinegård, D Oldberg, Å 

作者机构：Univ Lund Dept Cell & Mol Biol S-22100 Lund Sweden Univ Lund Hosp Dept Expt Pathol S-22185 Lund Sweden Natl Hosp Norway Dept Pathol Lab Electron Microscopy N-0027 Oslo Norway 

出 版 物：《JOURNAL OF BIOLOGICAL CHEMISTRY》 (生物化学杂志)

年 卷 期：1999年第274卷第14期

页      面：9636-9647页

核心收录：

学科分类：0710[理学-生物学] 071010[理学-生物化学与分子生物学] 081704[工学-应用化学] 07[理学] 08[工学] 0817[工学-化学工程与技术] 

主　　题：载体蛋白质类/遗传学 载体蛋白质类/生理学 细胞系 硫酸软骨素蛋白聚糖类/代谢 胶原 结缔组织/畸形 细胞外基质蛋白质类 免疫组织化学 原位杂交 硫酸角质素/代谢 小鼠 基因敲除 显微镜检查 电子 蛋白聚糖类 RNA 信使/代谢 腱/畸形 腱/代谢 动物 小鼠 

摘      要：Fibromodulin is a member of a family of connective tissue glycoproteins/proteoglycans containing leucine-rich repeat motifs. Several members of this gene family bind to fibrillar collagens and are believed to function in the assembly of the collagen network in connective tissues. Here we show that mice lacking a functional fibromodulin gene exhibit an altered morphological phenotype in tail tendon with fewer and abnormal collagen fiber bundles. In fibromodulin-null animals virtually all collagen fiber bundles are disorganized and have an abnormal morphology. Also 10-20% of the bundles in heterozygous mice are similar to the abnormal bundles in fibromodulin-null tail tendon. Ultrastructural analysis of Achilles tendon from fibromodulin-null mice show collagen fibrils with irregular and rough outlines in cross-section. Morphometric analysis show that fibromodulin-null mice have on the average thinner fibrils than wild type animals as a result of a larger preponderance of very thin fibrils in an overall similar range of fibril diameters. Protein and RNA analyses show an approximately 4-fold increase in the content of lumican in fibromodulin-null as compared with wild type tail tendon, despite a decrease in lumican mRNA These results demonstrate a role for fibromodulin in collagen fibrillogenesis and suggest that the orchestrated action of several leucine-rich repeat glycoproteins/proteoglycans influence the architecture of collagen matrices.