• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of biochemjBJ Latest papers and much more!
Biochem J. Dec 15, 1986; 240(3): 699–708.
PMCID: PMC1147476

Collagen defects in lethal perinatal osteogenesis imperfecta.


Quantitative and qualitative abnormalities of collagen were observed in tissues and fibroblast cultures from 17 consecutive cases of lethal perinatal osteogenesis imperfecta (OI). The content of type I collagen was reduced in OI dermis and bone and the content of type III collagen was also reduced in the dermis. Normal bone contained 99.3% type I and 0.7% type V collagen whereas OI bone contained a lower proportion of type I, a greater proportion of type V and a significant amount of type III collagen. The type III and V collagens appeared to be structurally normal. In contrast, abnormal type I collagen chains, which migrated slowly on electrophoresis, were observed in all babies with OI. Cultured fibroblasts from five babies produced a mixture of normal and abnormal type I collagens; the abnormal collagen was not secreted in two cases and was slowly secreted in the others. Fibroblasts from 12 babies produced only abnormal type I collagens and they were also secreted slowly. The slower electrophoretic migration of the abnormal chains was due to enzymic overmodification of the lysine residues. The distribution of the cyanogen bromide peptides containing the overmodified residues was used to localize the underlying structural abnormalities to three regions of the type I procollagen chains. These regions included the carboxy-propeptide of the pro alpha 1(I)-chain, the helical alpha 1(I) CB7 peptide and the helical alpha 1(I) CB8 and CB3 peptides. In one baby a basic charge mutation was observed in the alpha 1(I) CB7 peptide and in another baby a basic charge mutation was observed in the alpha 1(I) CB8 peptide. The primary defects in lethal perinatal OI appear to reside in the type I collagen chains. Type III and V collagens did not appear to compensate for the deficiency of type I collagen in the tissues.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (2.4M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Banes AJ, Yamauchi M, Mechanic GL. Nonmineralized and mineralized compartments of bone: the role of pyridinoline in nonmineralized collagen. Biochem Biophys Res Commun. 1983 Jun 29;113(3):975–981. [PubMed]
  • Barsh GS, David KE, Byers PH. Type I osteogenesis imperfecta: a nonfunctional allele for pro alpha 1 (I) chains of type I procollagen. Proc Natl Acad Sci U S A. 1982 Jun;79(12):3838–3842. [PMC free article] [PubMed]
  • Bateman JF, Mascara T, Chan D, Cole WG. Abnormal type I collagen metabolism by cultured fibroblasts in lethal perinatal osteogenesis imperfecta. Biochem J. 1984 Jan 1;217(1):103–115. [PMC free article] [PubMed]
  • Bateman JF, Mascara T, Chan D, Cole WG. Rapid fractionation of collagen chains and peptides by high-performance liquid chromatography. Anal Biochem. 1986 Apr;154(1):338–344. [PubMed]
  • Bonadio J, Holbrook KA, Gelinas RE, Jacob J, Byers PH. Altered triple helical structure of type I procollagen in lethal perinatal osteogenesis imperfecta. J Biol Chem. 1985 Feb 10;260(3):1734–1742. [PubMed]
  • Bonner WM, Laskey RA. A film detection method for tritium-labelled proteins and nucleic acids in polyacrylamide gels. Eur J Biochem. 1974 Jul 1;46(1):83–88. [PubMed]
  • Burgeson RE, El Adli FA, Kaitila II, Hollister DW. Fetal membrane collagens: identification of two new collagen alpha chains. Proc Natl Acad Sci U S A. 1976 Aug;73(8):2579–2583. [PMC free article] [PubMed]
  • Chan D, Cole WG. Quantitation of type I and III collagens using electrophoresis of alpha chains and cyanogen bromide peptides. Anal Biochem. 1984 Jun;139(2):322–328. [PubMed]
  • ChandraRajan J. Separation of type III collagen from type I collagen and pepsin by differential denaturation and renaturation. Biochem Biophys Res Commun. 1978 Jul 14;83(1):180–186. [PubMed]
  • Cheung DT, Benya PD, Hofer DP, Nimni ME. The use of 2-dimensional CNBr peptide maps for the analysis of crosslinked peptides in bone collagen. Coll Relat Res. 1981 Apr;1(3):247–256. [PubMed]
  • Cheung DT, DiCesare P, Benya PD, Libaw E, Nimni ME. The presence of intermolecular disulfide cross-links in type III collagen. J Biol Chem. 1983 Jun 25;258(12):7774–7778. [PubMed]
  • Cole WG, Chan D. Analysis of the heterogeneity of human collagens by two-dimensional polyacrylamide-gel electrophoresis. Biochem J. 1981 Aug 1;197(2):377–383. [PMC free article] [PubMed]
  • Cole WG, Chan D, Hickey AJ, Wilcken DE. Collagen composition of normal and myxomatous human mitral heart valves. Biochem J. 1984 Apr 15;219(2):451–460. [PMC free article] [PubMed]
  • Epstein EH., Jr (Alpha1(3))3 human skin collagen. Release by pepsin digestion and preponderance in fetal life. J Biol Chem. 1974 May 25;249(10):3225–3231. [PubMed]
  • Fujii K, Tanzer ML. Osteogenesis imperfecta: biochemical studies of bone collagen. Clin Orthop Relat Res. 1977 May;(124):271–277. [PubMed]
  • Gollwitzer R, Timpl R, Becker U, Furthmayr H. Chemical and immunological properties of reduced and alkylated polypeptide chains of bovine fibrinogen. Eur J Biochem. 1972 Aug 4;28(4):497–506. [PubMed]
  • JACKSON DS, BENTLEY JP. On the significance of the extractable collagens. J Biophys Biochem Cytol. 1960 Feb;7:37–42. [PMC free article] [PubMed]
  • Jamall IS, Finelli VN, Que Hee SS. A simple method to determine nanogram levels of 4-hydroxyproline in biological tissues. Anal Biochem. 1981 Mar 15;112(1):70–75. [PubMed]
  • Kirsch E, Glanville RW, Krieg T, Müller P. Analysis of cyanogen bromide peptides of type I collagen from a patient with lethal osteogenesis imperfecta. Biochem J. 1983 Jun 1;211(3):599–603. [PMC free article] [PubMed]
  • Kuboki Y, Tsuzaki M, Sasaki S, Liu CF, Mechanic GL. Location of the intermolecular cross-links in bovine dentin collagen, solubilization with trypsin and isolation of cross-link peptides containing dihydroxylysinonorleucine and pyridinoline. Biochem Biophys Res Commun. 1981 Sep 16;102(1):119–126. [PubMed]
  • Light ND, Bailey AJ. Changes in crosslinking during aging in bovine tendon collagen. FEBS Lett. 1979 Jan 1;97(1):183–188. [PubMed]
  • Ornoy A, Kim OJ. Scanning electron microscopy findings in osteogenesis imperfecta fetalis. Isr J Med Sci. 1977 Jan;13(1):26–32. [PubMed]
  • Petrovic OM, Miller EJ. An unusual pattern of peptide-bound lysine metabolism in collagen from an infant with lethal perinatal osteogenesis imperfecta. J Clin Invest. 1984 Jun;73(6):1569–1575. [PMC free article] [PubMed]
  • PIEZ KA, WEISS E, LEWIS MS. The separation and characterization of the alpha- and beta-components of calf skin collagen. J Biol Chem. 1960 Jul;235:1987–1991. [PubMed]
  • Pope FM, Nicholls AC, Eggleton C, Narcissi P, Hey EN, Parkin JM. Osteogenesis imperfecta (lethal) bones contain types III and V collagens. J Clin Pathol. 1980 Jun;33(6):534–538. [PMC free article] [PubMed]
  • Prockop DJ. Osteogenesis imperfecta: phenotypic heterogeneity, protein suicide, short and long collagen. Am J Hum Genet. 1984 May;36(3):499–505. [PMC free article] [PubMed]
  • Prockop DJ, Kivirikko KI. Heritable diseases of collagen. N Engl J Med. 1984 Aug 9;311(6):376–386. [PubMed]
  • Rowe DW, Shapiro JR, Poirier M, Schlesinger S. Diminished type I collagen synthesis and reduced alpha 1(I) collagen messenger RNA in cultured fibroblasts from patients with dominantly inherited (type I) osteogenesis imperfecta. J Clin Invest. 1985 Aug;76(2):604–611. [PMC free article] [PubMed]
  • Scott PG, Veis A. The cyanogen bromide peptides of bovine soluble and insoluble collagens. I. Characterization of peptides from soluble type I collagen by sodium dodecylsulphate polyacrylamide gel electrophoresis. Connect Tissue Res. 1976;4(2):107–116. [PubMed]
  • Sillence DO, Senn A, Danks DM. Genetic heterogeneity in osteogenesis imperfecta. J Med Genet. 1979 Apr;16(2):101–116. [PMC free article] [PubMed]
  • Sykes B, Puddle B, Francis M, Smith R. The estimation of two collagens from human dermis by interrupted gel electrophoresis. Biochem Biophys Res Commun. 1976 Oct 18;72(4):1472–1480. [PubMed]
  • Trelstad RL, Rubin D, Gross J. Osteogenesis imperfecta congenita: evidence for a generalized molecular disorder of collagen. Lab Invest. 1977 May;36(5):501–508. [PubMed]
  • van der Rest M, Fietzek PP. A comprehensive approach to the study of collagen primary structure based on high-performance liquid chromatography. Eur J Biochem. 1982 Jul;125(3):491–496. [PubMed]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • Compound
    PubChem Compound links
  • MedGen
    Related information in MedGen
  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...