Abstract

The purpose of this program is to bring together several independent investigators so that they can take advantage of an unusual opportunity both to advance the basic information we have about the biology of connective tissues and to explore the possible implications that this information may have for our understanding of diseases which affect these tissues. A major part of the work on diseases will focus on the relatively well-defined genetic diseases osteogenesis imperfecta and Ehlers-Danlos syndrome. These diseases will be studied both because of their own intrinsic importance and because of the implications that several recent discoveries about these diseases have for more common conditions such as osteoporosis, osteoarthritis, diabetes and related disorders. The research will include collaborative studies in the following specific areas: Studies on the enzyme which cleaves the N-terminal propeptide in the conversion of procollagen to collagen (CO1); studies on the enzyme which cleaves the C-terminal propeptide in the conversion of procollagen to collagen (CO2); formation of collagen fibers in vitro by the enzymatic cleavage of procollagen (CO3); structure and function of altered procollagens synthesized by fibroblasts from patients with osteogenesis imperfecta and related disorders (CO5).

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Program Projects (P01)
Project #
5P01AR038188-04
Application #
3092382
Study Section
(SRC)
Project Start
1986-04-01
Project End
1989-08-31
Budget Start
1988-09-01
Budget End
1989-08-31
Support Year
4
Fiscal Year
1988
Total Cost
Indirect Cost

  Institution

Name
Thomas Jefferson University
Department
Type
Schools of Medicine
DUNS #
061197161
City
Philadelphia
State
PA
Country
United States
Zip Code
19107

  Publications

Yuan, C M; Ala-Kokko, L; Le Guellec, D et al. (2000) Lack of a phenotype in transgenic mice aberrantly expressing COL2A1 mRNA because of highly selective post-transcriptional down-regulation. Biochem J 345 Pt 2:377-84
Devoto, M; Shimoya, K; Caminis, J et al. (1998) First-stage autosomal genome screen in extended pedigrees suggests genes predisposing to low bone mineral density on chromosomes 1p, 2p and 4q. Eur J Hum Genet 6:151-7
Kuivaniemi, H; Tromp, G; Prockop, D J (1997) Mutations in fibrillar collagens (types I, II, III, and XI), fibril-associated collagen (type IX), and network-forming collagen (type X) cause a spectrum of diseases of bone, cartilage, and blood vessels. Hum Mutat 9:300-15
Li, S W; Sieron, A L; Fertala, A et al. (1996) The C-proteinase that processes procollagens to fibrillar collagens is identical to the protein previously identified as bone morphogenic protein-1. Proc Natl Acad Sci U S A 93:5127-30
Zhuang, J; Tromp, G; Kuivaniemi, H et al. (1996) Direct sequencing of PCR products derived from cDNAs for the pro alpha 1 and pro alpha 2 chains of type I procollagen as a screening method to detect mutations in patients with osteogenesis imperfecta. Hum Mutat 7:89-99
Zhuang, J; Tromp, G; Kuivaniemi, H et al. (1996) Substitution of arginine for glycine at position 154 of the alpha 1 chain of type I collagen in a variant of osteogenesis imperfecta: comparison to previous cases with the same mutation. Am J Med Genet 61:111-16
Spotila, L D; Caminis, J; Devoto, M et al. (1996) Osteopenia in 37 members of seven families: analysis based on a model of dominant inheritance. Mol Med 2:313-24
Li, S W; Nembhard, K M; Prockop, D J et al. (1996) Identification and cloning of integration site of DNA by PCR. Biotechniques 20:356-8
Williams, C J; Ganguly, A; Considine, E et al. (1996) A-2-->G transition at the 3' acceptor splice site of IVS17 characterizes the COL2A1 gene mutation in the original Stickler syndrome kindred. Am J Med Genet 63:461-7
Spotila, L D; Caminis, J; Johnston, R et al. (1996) Vitamin D receptor genotype is not associated with bone mineral density in three ethnic/regional groups. Calcif Tissue Int 59:235-7

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