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

Fibromodulin is a member of a family of connective tissue glycoproteins/pro teoglycans containing leucine-rich repeat motifs. Several members of this g ene family bind to fibrillar collagens and are believed to function in the assembly of the collagen network in connective tissues. Here we show that m ice lacking a functional fibromodulin gene exhibit an altered morphological phenotype in tail tendon with fewer and abnormal collagen fiber bundles. I n fibromodulin-null animals virtually all collagen fiber bundles are disorg anized and have an abnormal morphology. Also 10-20% of the bundles in heter ozygous 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-secti on. Morphometric analysis show that fibromodulin-null mice have on the aver age thinner fibrils than wild type animals as a result of a larger preponde rance of very thin fibrils in an overall similar range of fibril diameters. Protein and RNA analyses show an approximately 4-fold increase in the cont ent of lumican in fibromodulin-null as compared with wild type tail tendon, despite a decrease in lumican mRNA These results demonstrate a role for fi bromodulin in collagen fibrillogenesis and suggest that the orchestrated ac tion of several leucine-rich repeat glycoproteins/proteoglycans influence t he architecture of collagen matrices.