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. 1992 Nov;11(11):3857–3863. doi: 10.1002/j.1460-2075.1992.tb05478.x

Molecular analysis of mutations in the Caenorhabditis elegans collagen gene dpy-7.

I L Johnstone 1, Y Shafi 1, J D Barry 1
PMCID: PMC556895  PMID: 1396579

Abstract

Collagens are a family of proteins contributing to the body structure of eukaryotes. They are encoded by a large and diverse gene family in the nematode Caenorhabditis elegans but by only a few genes in vertebrates. We have studied mutant alleles of the C. elegans dpy-7 gene, one of a large group of genes whose mutant phenotype is altered body form and several of which have previously been shown to encode cuticular collagens. We made use of the C. elegans physical map to screen specifically for collagen genes in the region of the X chromosome to which dpy-7 maps. This yielded a wild-type collagen gene clone which we showed, by micro-injection, could repair the dpy-7 mutant phenotype in transgenic animals. We cloned the homologous sequence from four dpy-7 mutant strains and by sequence analysis identified a single mutation in each case. All four mutations result in the substitution of a glycine with a larger residue in the conserved Gly-X-Y collagen domains. Similar substitutions in vertebrate collagens cause the heritable brittle bone disorder osteogenesis imperfecta. Whereas the human mutations are dominant, the dpy-7 mutations are recessive, and this may reflect different levels of complexity of collagenous macromolecular structures in the two organisms.

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Selected References

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

  1. Barstead R. J., Waterston R. H. The basal component of the nematode dense-body is vinculin. J Biol Chem. 1989 Jun 15;264(17):10177–10185. [PubMed] [Google Scholar]
  2. Birnstiel M. L., Busslinger M., Strub K. Transcription termination and 3' processing: the end is in site! Cell. 1985 Jun;41(2):349–359. doi: 10.1016/s0092-8674(85)80007-6. [DOI] [PubMed] [Google Scholar]
  3. Brenner S. The genetics of Caenorhabditis elegans. Genetics. 1974 May;77(1):71–94. doi: 10.1093/genetics/77.1.71. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Byers P. H. Brittle bones--fragile molecules: disorders of collagen gene structure and expression. Trends Genet. 1990 Sep;6(9):293–300. doi: 10.1016/0168-9525(90)90235-x. [DOI] [PubMed] [Google Scholar]
  5. Coulson A., Sulston J., Brenner S., Karn J. Toward a physical map of the genome of the nematode Caenorhabditis elegans. Proc Natl Acad Sci U S A. 1986 Oct;83(20):7821–7825. doi: 10.1073/pnas.83.20.7821. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cox G. N., Carr S., Kramer J. M., Hirsh D. Genetic mapping of Caenorhabditis elegans collagen genes using DNA polymorphisms as phenotypic markers. Genetics. 1985 Mar;109(3):513–528. doi: 10.1093/genetics/109.3.513. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Cox G. N., Fields C., Kramer J. M., Rosenzweig B., Hirsh D. Sequence comparisons of developmentally regulated collagen genes of Caenorhabditis elegans. Gene. 1989;76(2):331–344. doi: 10.1016/0378-1119(89)90173-x. [DOI] [PubMed] [Google Scholar]
  8. Cox G. N., Hirsh D. Stage-specific patterns of collagen gene expression during development of Caenorhabditis elegans. Mol Cell Biol. 1985 Feb;5(2):363–372. doi: 10.1128/mcb.5.2.363. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Cox G. N., Kramer J. M., Hirsh D. Number and organization of collagen genes in Caenorhabditis elegans. Mol Cell Biol. 1984 Nov;4(11):2389–2395. doi: 10.1128/mcb.4.11.2389. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Cox G. N., Kusch M., Edgar R. S. Cuticle of Caenorhabditis elegans: its isolation and partial characterization. J Cell Biol. 1981 Jul;90(1):7–17. doi: 10.1083/jcb.90.1.7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Cox G. N., Laufer J. S., Kusch M., Edgar R. S. Genetic and Phenotypic Characterization of Roller Mutants of CAENORHABDITIS ELEGANS. Genetics. 1980 Jun;95(2):317–339. doi: 10.1093/genetics/95.2.317. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Cox G. N., Staprans S., Edgar R. S. The cuticle of Caenorhabditis elegans. II. Stage-specific changes in ultrastructure and protein composition during postembryonic development. Dev Biol. 1981 Sep;86(2):456–470. doi: 10.1016/0012-1606(81)90204-9. [DOI] [PubMed] [Google Scholar]
  13. Devereux J., Haeberli P., Smithies O. A comprehensive set of sequence analysis programs for the VAX. Nucleic Acids Res. 1984 Jan 11;12(1 Pt 1):387–395. doi: 10.1093/nar/12.1part1.387. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Engel J., Prockop D. J. The zipper-like folding of collagen triple helices and the effects of mutations that disrupt the zipper. Annu Rev Biophys Biophys Chem. 1991;20:137–152. doi: 10.1146/annurev.bb.20.060191.001033. [DOI] [PubMed] [Google Scholar]
  15. Fessler J. H., Fessler L. I. Biosynthesis of procollagen. Annu Rev Biochem. 1978;47:129–162. doi: 10.1146/annurev.bi.47.070178.001021. [DOI] [PubMed] [Google Scholar]
  16. Fire A. Integrative transformation of Caenorhabditis elegans. EMBO J. 1986 Oct;5(10):2673–2680. doi: 10.1002/j.1460-2075.1986.tb04550.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Higgins B. J., Hirsh D. Roller mutants of the nematode Caenorhabditis elegans. Mol Gen Genet. 1977 Jan 7;150(1):63–72. doi: 10.1007/BF02425326. [DOI] [PubMed] [Google Scholar]
  18. Kramer J. M., Cox G. N., Hirsh D. Comparisons of the complete sequences of two collagen genes from Caenorhabditis elegans. Cell. 1982 Sep;30(2):599–606. doi: 10.1016/0092-8674(82)90256-2. [DOI] [PubMed] [Google Scholar]
  19. Kramer J. M., Cox G. N., Hirsh D. Expression of the Caenorhabditis elegans collagen genes col-1 and col-2 is developmentally regulated. J Biol Chem. 1985 Feb 10;260(3):1945–1951. [PubMed] [Google Scholar]
  20. Kramer J. M., French R. P., Park E. C., Johnson J. J. The Caenorhabditis elegans rol-6 gene, which interacts with the sqt-1 collagen gene to determine organismal morphology, encodes a collagen. Mol Cell Biol. 1990 May;10(5):2081–2089. doi: 10.1128/mcb.10.5.2081. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Kramer J. M., Johnson J. J., Edgar R. S., Basch C., Roberts S. The sqt-1 gene of C. elegans encodes a collagen critical for organismal morphogenesis. Cell. 1988 Nov 18;55(4):555–565. doi: 10.1016/0092-8674(88)90214-0. [DOI] [PubMed] [Google Scholar]
  22. Krause M., Hirsh D. A trans-spliced leader sequence on actin mRNA in C. elegans. Cell. 1987 Jun 19;49(6):753–761. doi: 10.1016/0092-8674(87)90613-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Kusch M., Edgar R. S. Genetic studies of unusual loci that affect body shape of the nematode Caenorhabditis elegans and may code for cuticle structural proteins. Genetics. 1986 Jul;113(3):621–639. doi: 10.1093/genetics/113.3.621. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Mello C. C., Kramer J. M., Stinchcomb D., Ambros V. Efficient gene transfer in C.elegans: extrachromosomal maintenance and integration of transforming sequences. EMBO J. 1991 Dec;10(12):3959–3970. doi: 10.1002/j.1460-2075.1991.tb04966.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Ouazana R., Herbage D. Biochemical characterization of the cuticle collagen of the nematode Caenorhabditis elegans. Biochim Biophys Acta. 1981 Jul 28;669(2):236–243. doi: 10.1016/0005-2795(81)90246-4. [DOI] [PubMed] [Google Scholar]
  26. Park Y. S., Kramer J. M. Tandemly duplicated Caenorhabditis elegans collagen genes differ in their modes of splicing. J Mol Biol. 1990 Jan 20;211(2):395–406. doi: 10.1016/0022-2836(90)90360-X. [DOI] [PubMed] [Google Scholar]
  27. Prockop D. J. Seminars in medicine of the Beth Israel Hospital, Boston. Mutations in collagen genes as a cause of connective-tissue diseases. N Engl J Med. 1992 Feb 20;326(8):540–546. doi: 10.1056/NEJM199202203260807. [DOI] [PubMed] [Google Scholar]
  28. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
  30. von Mende N., Bird D. M., Albert P. S., Riddle D. L. dpy-13: a nematode collagen gene that affects body shape. Cell. 1988 Nov 18;55(4):567–576. doi: 10.1016/0092-8674(88)90215-2. [DOI] [PubMed] [Google Scholar]

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