The aims of this project are (1) to use animal models with heriditary defects in collagen fibrillogenesis to study the regulation of the packing of collagen into fibrils, (2) to correlate the results of microscopic and biochemical analysis of abnormalities in collagen to the results of quantitative analyses of changes in the physical properties of skin and bone; and (3) to supply other research laboratories with well characterized animal models for basic studies of different defects in collagen fibrillogenesis. Six unrelated cats and three unrelated dogs with hyperextensible fragile skin have been shown to have different microscopic defects in collagen fibrils and fibers in the skin. Genetic studies of two of these cats and two of the dogs show that these defects are each transmitted as a simple autosomal sominant trait. Electron microscopic abnormalities in the collagen fibrils and fibers are identical in each related animal but are different in unrelated animals. This suggests that each of these defects may be due to a different defect in a single structural protein. Therefore, pairs of affected and unaffected animals are used (1) for bright field and polarized light microscopy, scanning and transmission electron microscopy and x-ray crystallography of the packing of collagen in skin, tendon and bone, (2) for quantitative biochemical analysis of the peptide chains of type I, type III and type V procollagens and collagens in skin and bone, (3) for in vivo and in vitro studies of the synthesis and degradation of the different types of collagen in skin, (4) for immunofluorescent and immunoelectron microscopic studies of the distribution of different extracellular matrix components in skin, and (5) for mechanical studies of changes in the physical properties of skin and bone that result from differences in the amounts and organization of collagen in these tissues. These studies will permit us to understand the mechanisms that control collagen fibrillogenesis in the developing embryo, during growth and maturation, during wound healing, and in diseases such as the Ehlers-Danlos syndrome in man.
| Minor, R R; Farnum, C E (1988) Animal models with chondrodysplasia/osteochondrodysplasia. Pathol Immunopathol Res 7:62-7 |
| D'Amico-Martel, A; Van de Water, T R; Wootton, J A et al. (1987) Changes in the types of collagen synthesized during chondrogenesis of the mouse otic capsule. Dev Biol 120:542-55 |
| Minor, R R; Wootton, J A; Prockop, D J et al. (1987) Genetic diseases of connective tissues in animals. Curr Probl Dermatol 17:199-215 |
| Minor, R R; Sippola-Thiele, M; McKeon, J et al. (1986) Defects in the processing of procollagen to collagen are demonstrable in cultured fibroblasts from patients with the Ehlers-Danlos and osteogenesis imperfecta syndromes. J Biol Chem 261:10006-14 |
| Abergel, R P; Pizzurro, D; Meeker, C A et al. (1985) Biochemical composition of the connective tissue in keloids and analysis of collagen metabolism in keloid fibroblast cultures. J Invest Dermatol 84:384-90 |
