Type V collagen controls the initiation of collagen fibril assembly.
Vertebrate collagen fibrils are heterotypically composed of a quantitatively major and minor fibril collagen. In non-cartilaginous tissues, type I collagen accounts for the majority of the collagen mass, and collagen type V, the functions of which are poorly understood, is a minor component. Type V collagen has been implicated in the regulation of fibril diameter, and we reported recently preliminary evidence that type V collagen is required for collagen fibril nucleation (Wenstrup, R. J., Florer, J. B., Cole, W. G., Willing, M. C., and Birk, D. E. (2004) J. Cell. Biochem. 92, 113-124). The purpose of this study was to define the roles of type V collagen in the regulation of collagen fibrillogenesis and matrix assembly. Mouse embryos completely deficient in pro-alpha1(V) chains were created by homologous recombination. The col5a1-/- animals die in early embryogenesis, at approximately embryonic day 10. The type V collagen-deficient mice demonstrate a virtual lack of collagen fibril formation. In contrast, the col5a1+/- animals are viable. The reduced type V collagen content is associated with a 50% reduction in fibril number and dermal collagen content. In addition, relatively normal, cylindrical fibrils are assembled with a second population of large, structurally abnormal collagen fibrils. The structural properties of the abnormal matrix are decreased relative to the wild type control animals. These data indicate a central role for the evolutionary, ancient type V collagen in the regulation of fibrillogenesis. The complete dependence of fibril formation on type V collagen is indicative of the critical role of the latter in early fibril initiation. In addition, this fibril collagen is important in the determination of fibril structure and matrix organization.
Wenstrup
Richard J
RJ
Division of Human Genetics, Cincinnati Children's Hospital Research Foundation, 3333 Burnet Ave., ML 4006, Cincinnati, OH 45229, USA. richard.wenstrup@cchmc.org
Florer
Jane B
JB
Brunskill
Eric W
EW
Bell
Sheila M
SM
Chervoneva
Inna
I
Birk
David E
DE
D000818:Animals; D015153:Blotting, Western; D018929:Cell Culture Techniques; D003094:Collagen / Q000737:chemistry / Q000378:metabolism; D024062:Collagen Type V / Q000737:chemistry / Q000502:physiology*; D004247:DNA / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D004622:Embryo, Mammalian / Q000378:metabolism; D005091:Exons; D005109:Extracellular Matrix / Q000378:metabolism; D005822:Genetic Vectors; D005838:Genotype; D017403:In Situ Hybridization; D051379:Mice; D008854:Microscopy, Electron; D046529:Microscopy, Electron, Transmission; D008954:Models, Biological; D008957:Models, Genetic; D012867:Skin / Q000378:metabolism; D013997:Time Factors
D024062:Collagen Type V; D003094:Collagen; D004247:DNA