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. 1987 Jun 1;244(2):375–379. doi: 10.1042/bj2440375

Collagen synthesis by cell lines derived from Mov-13 mouse embryos which have a lethal mutation in the collagen alpha 1(I) gene.

M Dziadek 1, R Timpl 1, R Jaenisch 1
PMCID: PMC1148001  PMID: 3663130

Abstract

Mouse embryos homozygous for the Mov-13 mutation produce no collagen I, owing to transcriptional blockage of the collagen alpha 1(I) gene by a retroviral insert. Fibroblast-like cell lines derived from these embryos were compared with similar lines derived from heterozygous and wild-type embryos with respect to the total amounts, and types, of collagen synthesized. Total collagen synthesized by either cloned or uncloned cell lines correlated with their genotype, demonstrating no compensation for absence of collagen I production by an increase in synthesis of other collagen types. Procollagen alpha 2(I) chains were not detected in the homozygous cell lines, demonstrating that these chains do not form homotrimers, nor do they form heterotrimers with alpha-chains of other collagen types. Procollagen III levels were quantified by radioimmunoassay and found to be similar in all cell lines.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aumailley M., Krieg T., Razaka G., Müller P. K., Bricaud H. Influence of cell density on collagen biosynthesis in fibroblast cultures. Biochem J. 1982 Sep 15;206(3):505–510. doi: 10.1042/bj2060505. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bienkowski R. S. Intracellular degradation of newly synthesized collagen. Coll Relat Res. 1984 Oct;4(5):399–411. doi: 10.1016/s0174-173x(84)80008-4. [DOI] [PubMed] [Google Scholar]
  3. Bonner W. M., Laskey R. A. A film detection method for tritium-labelled proteins and nucleic acids in polyacrylamide gels. Eur J Biochem. 1974 Jul 1;46(1):83–88. doi: 10.1111/j.1432-1033.1974.tb03599.x. [DOI] [PubMed] [Google Scholar]
  4. Bordin S., Page R. C., Narayanan A. S. Heterogeneity of normal human diploid fibroblasts: isolation and characterization of one phenotype. Science. 1984 Jan 13;223(4632):171–173. doi: 10.1126/science.6691142. [DOI] [PubMed] [Google Scholar]
  5. Bornstein P., Sage H. Structurally distinct collagen types. Annu Rev Biochem. 1980;49:957–1003. doi: 10.1146/annurev.bi.49.070180.004521. [DOI] [PubMed] [Google Scholar]
  6. Breindl M., Harbers K., Jaenisch R. Retrovirus-induced lethal mutation in collagen I gene of mice is associated with an altered chromatin structure. Cell. 1984 Aug;38(1):9–16. doi: 10.1016/0092-8674(84)90521-x. [DOI] [PubMed] [Google Scholar]
  7. Chu M. L., Rowe D., Nicholls A. C., Pope F. M., Prockop D. J. Presence of translatable mRNA for pro alpha 2(I) chains in fibroblasts from a patient with osteogenesis imperfecta whose type I collagen does not contain alpha 2(I) chains. Coll Relat Res. 1984 Oct;4(5):389–394. doi: 10.1016/s0174-173x(84)80006-0. [DOI] [PubMed] [Google Scholar]
  8. Hartung S., Jaenisch R., Breindl M. Retrovirus insertion inactivates mouse alpha 1(I) collagen gene by blocking initiation of transcription. 1986 Mar 27-Apr 2Nature. 320(6060):365–367. doi: 10.1038/320365a0. [DOI] [PubMed] [Google Scholar]
  9. Jaenisch R., Harbers K., Schnieke A., Löhler J., Chumakov I., Jähner D., Grotkopp D., Hoffmann E. Germline integration of moloney murine leukemia virus at the Mov13 locus leads to recessive lethal mutation and early embryonic death. Cell. 1983 Jan;32(1):209–216. doi: 10.1016/0092-8674(83)90511-1. [DOI] [PubMed] [Google Scholar]
  10. Kratochwil K., Dziadek M., Löhler J., Harbers K., Jaenisch R. Normal epithelial branching morphogenesis in the absence of collagen I. Dev Biol. 1986 Oct;117(2):596–606. doi: 10.1016/0012-1606(86)90328-3. [DOI] [PubMed] [Google Scholar]
  11. Krieg T., Hörlein D., Wiestner M., Müller P. K. Aminoterminal extension peptides from type I procollagen normalize excessive collagen synthesis of scleroderma fibroblasts. Arch Dermatol Res. 1978 Nov 10;263(2):171–180. doi: 10.1007/BF00446438. [DOI] [PubMed] [Google Scholar]
  12. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  13. Löhler J., Timpl R., Jaenisch R. Embryonic lethal mutation in mouse collagen I gene causes rupture of blood vessels and is associated with erythropoietic and mesenchymal cell death. Cell. 1984 Sep;38(2):597–607. doi: 10.1016/0092-8674(84)90514-2. [DOI] [PubMed] [Google Scholar]
  14. Miller E. J., Rhodes R. K. Preparation and characterization of the different types of collagen. Methods Enzymol. 1982;82(Pt A):33–64. doi: 10.1016/0076-6879(82)82059-4. [DOI] [PubMed] [Google Scholar]
  15. Nicholls A. C., Pope F. M., Schloon H. Biochemical heterogeneity of osteogenesis imperfecta: New variant. Lancet. 1979 Jun 2;1(8127):1193–1193. doi: 10.1016/s0140-6736(79)91872-5. [DOI] [PubMed] [Google Scholar]
  16. Prockop D. J., Kivirikko K. I. Heritable diseases of collagen. N Engl J Med. 1984 Aug 9;311(6):376–386. doi: 10.1056/NEJM198408093110606. [DOI] [PubMed] [Google Scholar]
  17. Rohde H., Vargas L., Hahn E., Kalbfleisch H., Bruguera M., Timpl R. Radioimmunoassay for type III procollagen peptide and its application to human liver disease. Eur J Clin Invest. 1979 Dec;9(6):451–459. doi: 10.1111/j.1365-2362.1979.tb00912.x. [DOI] [PubMed] [Google Scholar]
  18. Schnieke A., Dziadek M., Bateman J., Mascara T., Harbers K., Gelinas R., Jaenisch R. Introduction of the human pro alpha 1(I) collagen gene into pro alpha 1(I)-deficient Mov-13 mouse cells leads to formation of functional mouse-human hybrid type I collagen. Proc Natl Acad Sci U S A. 1987 Feb;84(3):764–768. doi: 10.1073/pnas.84.3.764. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Schnieke A., Harbers K., Jaenisch R. Embryonic lethal mutation in mice induced by retrovirus insertion into the alpha 1(I) collagen gene. 1983 Jul 28-Aug 3Nature. 304(5924):315–320. doi: 10.1038/304315a0. [DOI] [PubMed] [Google Scholar]
  20. Timpl R. Antibodies to collagens and procollagens. Methods Enzymol. 1982;82(Pt A):472–498. doi: 10.1016/0076-6879(82)82079-x. [DOI] [PubMed] [Google Scholar]
  21. Tkocz C., Kühn K. The formation of triple-helical collagen molecules from alpha-1 or alpha-2 polypeptide chains. Eur J Biochem. 1969 Feb;7(4):454–462. doi: 10.1111/j.1432-1033.1969.tb19631.x. [DOI] [PubMed] [Google Scholar]
  22. Uitto J. Collagen polymorphism: isolation and partial characterization of alpha 1(I)-trimer molecules in normal human skin. Arch Biochem Biophys. 1979 Feb;192(2):371–379. doi: 10.1016/0003-9861(79)90105-x. [DOI] [PubMed] [Google Scholar]

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