Targeted disruption of dermatopontin causes abnormal collagen fibrillogenesis.

Gene targeting of a member of small leucine-rich repeat proteoglycans demonstrates that collagen fibrillogenesis is mediated by a set of extracellular matrix components, which interact with collagen. Collagen-associated protein dermatopontin knockout mice were generated in order to analyze the biologic involvement of dermatopontin in the formation of collagen fibrils. Although dermatopontin-null mice did not exhibit any obvious anatomical abnormality, skin elasticity was increased. Skin tensile tests revealed that the initial elastic modulus was 57% lower in dermatopontin-null mice than in wild-type mice, and that maximum tensile strength was similar. Remarkably, light microscopy study showed a significant decrease in the relative thickness of the dermis in dermatopontin-null mice compared with wild-type mice (45.2 +/- 3.09% and 57.8 +/- 4.25%, respectively). The skin collagen content was 40% lower in dermatopontin-null than in wild-type mice. Collagen fibrils in dermatopontin-null mice showed a great variety in diameter and irregular contours under the electron microscope. These data indicate that dermatopontin plays a critical role in elasticity of skin and collagen accumulation attributed to collagen fibrillogenesis in vivo.

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