Mutations in type 1 procollagen that cause osteogenesis imperfecta: effects of the mutations on the assembly of collagen into fibrils, the basis of phenotypic variations, and potential antisense therapies.
Prockop, D. J.; Colige, Alain; Helminen, H.et al.
1993 • In Journal of Bone and Mineral Research, 8 Suppl 2, p. 489-92
[en] Work by a large number of investigators over the last decade has established that over 90% of patients with osteogenesis imperfecta have mutations in one of the two genes for type I procollagen, that most unrelated probands have different mutations in the genes, and that the mutations found in most of the serious variants of the disease cause synthesis of abnormal pro alpha chains of the protein. The results have demonstrated that synthesis of structurally abnormal but partially functional pro alpha chains can interfere with folding of the central region of the protein into a triple-helical conformation, prevent processing of the N-terminal propeptides of procollagen, or produce subtle alterations in conformation that interfere with the self-assembly of the protein into collagen fibrils. One of the unsolved mysteries about the disease is why some mutations produce severe phenotypes, whereas very similar mutations produce mild phenotypes. Recent studies in transgenic mice suggest that nongenetic factors, such as stochastic events during development, may determine the severity of the disease phenotype produced by a specific mutation. Also, recent results raised the possibility that strategies of antisense gene therapy may be effective in treating the disease some time in the future. Specific inhibition of expression of a mutated collagen gene has been obtained with antisense oligonucleotides in cell culture experiments. However, there is no means of selective delivery of antisense oligonucleotides to the appropriate tissues.
Prockop, D. J.; Thomas Jefferson University, Philadelphia, Pennsylvania > Department of Biochemistry and Molecular Biology > Jefferson Institute of Molecular Medicine, Jefferson Medical College
Colige, Alain ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Laboratoire des tissus conjonctifs
Helminen, H.; Thomas Jefferson University, Philadelphia, Pennsylvania > Department of Biochemistry and Molecular Biology > Jefferson Institute of Molecular Medicine, Jefferson Medical College
Khillan, J. S.; Thomas Jefferson University, Philadelphia, Pennsylvania > Department of Biochemistry and Molecular Biology
Pereira, R.
Vandenberg, P.; Thomas Jefferson University, Philadelphia, Pennsylvania > Department of Biochemistry and Molecular Biology
Language :
English
Title :
Mutations in type 1 procollagen that cause osteogenesis imperfecta: effects of the mutations on the assembly of collagen into fibrils, the basis of phenotypic variations, and potential antisense therapies.
Publication date :
1993
Journal title :
Journal of Bone and Mineral Research
ISSN :
0884-0431
eISSN :
1523-4681
Publisher :
American Society for Bone and Mineral Research, Washington, United States - District of Columbia
Byers PH, Steiner RD (1992) Osteogenesis imperfecta. Annu Rev Med 43:269-289.
Kuivaniemi H, Tromp G, Prockop DJ (1991) Perspectives. Genetic causes of aortic aneurysms. J Clin Invest 88:1441-1444.
Prockop DJ (1990) Mutations that alter the primary structure of type I collagen. The perils of a system for generating large structures by the principle of nucleated growth. J Biol Chem 265:15349-15352.
Vogel BE, Doelz R, Kadler KE, Hojima Y, Engel J, Prockop DJ (1988) A substitution of cysteine for glycine 748 of the α1 chain produces a kink at this site in the procollagen I molecule and an altered N‐proteinase cleavage site over 225 nm away. J Biol Chem 263:19249-19255.
Kadler KE, Torre‐Blanco A, Adachi E, Vogel BE, Hojima Y, Prockop DJ (1991) A type I collagen with substitution of a cysteine for glycine‐748 in the αI(1) chain copolymerizes with normal type I collagen and can generate fractal‐like structures. Biochemistry 30:5081-5088.
Torre‐Blanco A, Adachi E, Romanic AM, Prockop DJ (1992) Copolymerization of normal type I collagen with three mutated type I collagens containing substitutions of cysteine at different glycine positions in the αI(I) chain. J Biol Chem 267:4968-4973.
Lightfoot SJ, Holmes DF, Brass A, Grant ME, Byers PH, Kadler KE (1992) Type I procollagens containing substitutions of aspartate, arginine, and cysteine for glycine in the proα,(I) chain are cleaved slowly by N‐proteinase, but only the cysteine substitution introduces a kink in the molecule. J Biol Chem 267:25521-25528.
Kadler KE, Hojima Y, Prockop DJ (1990) Collagen fibrils in vitro grow from pointed tips in the C‐to N‐terminal direction. Biochem J 268:339-343.
Holmes DF, Chapman JA, Prockop DJ, Kadler KE (1992) Growing tips of type I collagen fibrils formed in vitro are near‐paraboloidal in shape, implying a reciprocal relationship between accretion and diameter. Proc Natl Acad Sci USA 89:9855-9859.
Silver D, Miller J, Harrison R, Prockop DJ (1992) Helical model of nucleation and propagation to account for the growth of type I collagen fibrils from symmetrical pointed tips. A special example of self‐assembly of rod‐like monomers. Proc Natl Acad Sci USA 89:9860-9864.
Sippola M, Kaffe S, Prockop DJ (1984) A heterozygous defect for structurally altered proα2 chains of type I procollagen in a mild variant of osteogenesis imperfecta. The altered structure decreases the thermal stability of procollagen and makes it resistant to procollagen N‐proteinase. J Biol Chem 259:14094-14100.
de Vries WN, de Wet WJ, Cysteine in α1 chains of human type I collagen produces a clinical heterogeneous form of osteogenesis imperfecta. In: Senn A, Thornhill T (eds) UCLA Symposium on Molecular Biology and Cellular Biology–New Series, Vol. 45. Alan Liss, New York, pp; 1987, 56-64.
Khillan JS, Olsen AS, Kontusaari S, Sokolov B, Prockop DJ (1991) Transgenic mice that express a mini‐gene version of the human gene for type I procollagen (COLIAI) develop a phenotype resembling a lethal form of osteogenesis imperfecta. J Biol Chem 266:23373-23379.
Pereira R, Khillan JS, Helminen HJ, Hume EL, Prockop DJ (1993) Transgenic mice expressing a partially deleted gene for type I procollagen (COL1A1). A breeding line with a phenotype of spontaneous fractures and decreased bone collagen and mineral. J Clin Invest 91:709-716.
Vandenberg P, Khillan JS, Prockop DJ, Helminen H, Kontusaari S, Ala‐Kokko L (1991) Expression of a partially deleted gene of human type II procollagen (COL21) in transgenic mice produces a chondrodysplasia. Proc Natl Acad Sci USA 88:7640-7644.
Helminen HJ, Kiraly K, Pelttari A, Tammi MI, Vandenberg P, Pereira R, Dhulipata R, Bertolette D, Khillan JS, Hume EL, Prockop DJ (1993) Changes in cartilage and bone of transgenic mice expressing an internally deleted gene for human type II procollagen (COL2A1). Matrix 13:38.
Erickson RP, Izant JG Gene regulation: Biology of antisense RNA and DNA. Raven Press Series on Molecular and Cellular Biology , Raven Press, New York; 1992, 1.
Colige A, Baserga R, Prockop DJ (1993) Use of an antisense oligonucleotide to inhibit expression of a mutated human procollagen gene (COL1A1) in transfected mouse 3T3 cells. Biochemistry 32:7-11.