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.