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/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.
Svensson
L
L
Department of Cell and Molecular Biology, University of Lund, P.O. Box 94, S-221 00 Lund, Sweden.
Aszódi
A
A
Reinholt
F P
FP
Fässler
R
R
Heinegård
D
D
Oldberg
A
A
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D011508:Chondroitin Sulfate Proteoglycans / Q000378:metabolism*; D003094:Collagen; D003238:Connective Tissue / Q000002:abnormalities*; D016326:Extracellular Matrix Proteins; D000071235:Fibromodulin; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007632:Keratan Sulfate / Q000378:metabolism*; D000071234:Lumican; D051379:Mice; D018345:Mice, Knockout; D008854:Microscopy, Electron; D011509:Proteoglycans; D012333:RNA, Messenger / Q000378:metabolism; D013710:Tendons / Q000002:abnormalities / Q000378:metabolism*
D002352:Carrier Proteins; D011508:Chondroitin Sulfate Proteoglycans; D016326:Extracellular Matrix Proteins; C000604332:Fmod protein, mouse; C000604307:Lum protein, mouse; D000071234:Lumican; D011509:Proteoglycans; D012333:RNA, Messenger; D000071235:Fibromodulin; D003094:Collagen; D007632:Keratan Sulfate