TARGETED DISRUPTION OF DECORIN LEADS TO ABNORMAL COLLAGEN FIBRIL MORPHOLOGY AND SKIN FRAGILITY

Decorin is a member of the expanding group of widely distributed small leucine-rich proteoglycans that are expected to play important functi ons in tissue assembly. We report that mice harboring a targeted dis r uption of the decorin gene are viable but have fragile skin with marke dly reduced tensile strength. Ultrastructural analysis revealed abnorm al collagen morphology in skin and tendon, with coarser and irregular fiber outlines. Quantitative scanning transmission EM of individual co llagen fibrils showed abrupt increases and decreases in mass along the ir axes, thereby accounting for the irregular outlines and size variab ility observed in cross-sections. The data indicate uncontrolled later al fusion of collagen fibrils in the decorin-deficient mice and provid e an explanation for the reduced tensile strength of the skin, These f indings demonstrate a fundamental role for decorin in regulating colla gen fiber formation in vivo.