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.
Takeda
Ushio
U
Department of Clinical Biology of Extracellular Matrix, Graduate School of Medicine, Chiba University, Chiba, Japan.
Utani
Atsushi
A
Wu
Jinghai
J
Adachi
Eijiro
E
Koseki
Haruhiko
H
Taniguchi
Masaru
M
Matsumoto
Takeo
T
Ohashi
Toshiro
T
Sato
Masaaki
M
Shinkai
Hiroshi
H
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics*; D015815:Cell Adhesion Molecules / Q000235:genetics*; D011508:Chondroitin Sulfate Proteoglycans; D003094:Collagen / Q000378:metabolism* / Q000648:ultrastructure; D020405:Dermis / Q000378:metabolism / Q000473:pathology*; D004548:Elasticity; D005109:Extracellular Matrix / Q000378:metabolism* / Q000473:pathology; D016326:Extracellular Matrix Proteins; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008854:Microscopy, Electron; D016296:Mutagenesis / Q000502:physiology; D013718:Tensile Strength
D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; D011508:Chondroitin Sulfate Proteoglycans; C082019:DPT protein, human; C504453:Dpt protein, mouse; D016326:Extracellular Matrix Proteins; D003094:Collagen