Skip to main content
PMC home page
American Journal of Human Genetics logoLink to American Journal of Human Genetics
. 1991 Sep;49(3):545–554.

Sequence and localization of a partial cDNA encoding the human alpha 3 chain of type IV collagen.

K E Morrison 1, M Mariyama 1, T L Yang-Feng 1, S T Reeders 1
PMCID: PMC1683122  PMID: 1882840

Abstract

A novel type IV collagen, alpha 3(IV), has recently been identified in human and bovine basement membranes. Here we describe the cloning and sequencing of a cDNA encoding 218 residues of the NC1 domain of the human alpha 3(IV) chain. Of interest is the possible role of abnormalities of the alpha 3(IV) chain in Alport syndrome, as suggested by the failure to detect the NC1 domain of alpha 3(IV) in the basement membranes of some Alport syndrome patients. To determine whether the alpha 3(IV) gene (COL4A3) may be mutated in Alport syndrome, we localized it, by somatic cell hybrid analysis and in situ hybridization of metaphase chromosomes, to chromosome 2q35-2q37. Mutations in alpha 3(IV) cannot therefore be responsible for the vast majority of cases of Alport syndrome, which have been shown to be X linked. One explanation for the immunochemical data implicating alpha 3(IV) in Alport syndrome pathogenesis is that mutations of the alpha 5(IV) chain, which has been localized to Xq22 and found to be mutated in at least three kindreds with Alport syndrome, lead to failure to incorporate the alpha 3(IV) chains into the multimeric structure of glomerular basement membrane in a stable fashion.

Full text

PDF
545

Images in this article

550Figure 3
on p.550
551Figure 4
on p.551

Selected References

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

  1. Atkin C. L., Hasstedt S. J., Menlove L., Cannon L., Kirschner N., Schwartz C., Nguyen K., Skolnick M. Mapping of Alport syndrome to the long arm of the X chromosome. Am J Hum Genet. 1988 Feb;42(2):249–255. [PMC free article] [PubMed] [Google Scholar]
  2. Barker D. F., Hostikka S. L., Zhou J., Chow L. T., Oliphant A. R., Gerken S. C., Gregory M. C., Skolnick M. H., Atkin C. L., Tryggvason K. Identification of mutations in the COL4A5 collagen gene in Alport syndrome. Science. 1990 Jun 8;248(4960):1224–1227. doi: 10.1126/science.2349482. [DOI] [PubMed] [Google Scholar]
  3. Blumberg B., MacKrell A. J., Fessler J. H. Drosophila basement membrane procollagen alpha 1(IV). II. Complete cDNA sequence, genomic structure, and general implications for supramolecular assemblies. J Biol Chem. 1988 Dec 5;263(34):18328–18337. [PubMed] [Google Scholar]
  4. Brinker J. M., Gudas L. J., Loidl H. R., Wang S. Y., Rosenbloom J., Kefalides N. A., Myers J. C. Restricted homology between human alpha 1 type IV and other procollagen chains. Proc Natl Acad Sci U S A. 1985 Jun;82(11):3649–3653. doi: 10.1073/pnas.82.11.3649. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Brunner H., Schröder C., van Bennekom C., Lambermon E., Tuerlings J., Menzel D., Olbing H., Monnens L., Wieringa B., Ropers H. H. Localization of the gene for X-linked Alport's syndrome. Kidney Int. 1988 Oct;34(4):507–510. doi: 10.1038/ki.1988.210. [DOI] [PubMed] [Google Scholar]
  6. Butkowski R. J., Langeveld J. P., Wieslander J., Hamilton J., Hudson B. G. Localization of the Goodpasture epitope to a novel chain of basement membrane collagen. J Biol Chem. 1987 Jun 5;262(16):7874–7877. [PubMed] [Google Scholar]
  7. Butkowski R. J., Shen G. Q., Wieslander J., Michael A. F., Fish A. J. Characterization of type IV collagen NC1 monomers and Goodpasture antigen in human renal basement membranes. J Lab Clin Med. 1990 Mar;115(3):365–373. [PubMed] [Google Scholar]
  8. Butkowski R. J., Wieslander J., Wisdom B. J., Barr J. F., Noelken M. E., Hudson B. G. Properties of the globular domain of type IV collagen and its relationship to the Goodpasture antigen. J Biol Chem. 1985 Mar 25;260(6):3739–3747. [PubMed] [Google Scholar]
  9. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  10. Dion A. S., Myers J. C. COOH-terminal propeptides of the major human procollagens. Structural, functional and genetic comparisons. J Mol Biol. 1987 Jan 5;193(1):127–143. doi: 10.1016/0022-2836(87)90632-2. [DOI] [PubMed] [Google Scholar]
  11. Feinberg A. P., Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. doi: 10.1016/0003-2697(83)90418-9. [DOI] [PubMed] [Google Scholar]
  12. Flinter F. A., Abbs S., Bobrow M. Localization of the gene for classic Alport syndrome. Genomics. 1989 Apr;4(3):335–338. doi: 10.1016/0888-7543(89)90339-x. [DOI] [PubMed] [Google Scholar]
  13. Francke U., Yang-Feng T. L., Brissenden J. E., Ullrich A. Chromosomal mapping of genes involved in growth control. Cold Spring Harb Symp Quant Biol. 1986;51(Pt 2):855–866. doi: 10.1101/sqb.1986.051.01.099. [DOI] [PubMed] [Google Scholar]
  14. Hostikka S. L., Eddy R. L., Byers M. G., Höyhtyä M., Shows T. B., Tryggvason K. Identification of a distinct type IV collagen alpha chain with restricted kidney distribution and assignment of its gene to the locus of X chromosome-linked Alport syndrome. Proc Natl Acad Sci U S A. 1990 Feb;87(4):1606–1610. doi: 10.1073/pnas.87.4.1606. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Hostikka S. L., Tryggvason K. The complete primary structure of the alpha 2 chain of human type IV collagen and comparison with the alpha 1(IV) chain. J Biol Chem. 1988 Dec 25;263(36):19488–19493. [PubMed] [Google Scholar]
  16. Hudson B. G., Wieslander J., Wisdom B. J., Jr, Noelken M. E. Goodpasture syndrome: molecular architecture and function of basement membrane antigen. Lab Invest. 1989 Sep;61(3):256–269. [PubMed] [Google Scholar]
  17. Jenis E. H., Valeski J. E., Calcagno P. L. Variability of anti-GBM binding in hereditary nephritis. Clin Nephrol. 1981 Mar;15(3):111–114. [PubMed] [Google Scholar]
  18. Kashtan C., Fish A. J., Kleppel M., Yoshioka K., Michael A. F. Nephritogenic antigen determinants in epidermal and renal basement membranes of kindreds with Alport-type familial nephritis. J Clin Invest. 1986 Oct;78(4):1035–1044. doi: 10.1172/JCI112658. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Kleppel M. M., Kashtan C. E., Butkowski R. J., Fish A. J., Michael A. F. Alport familial nephritis. Absence of 28 kilodalton non-collagenous monomers of type IV collagen in glomerular basement membrane. J Clin Invest. 1987 Jul;80(1):263–266. doi: 10.1172/JCI113057. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Kleppel M. M., Kashtan C., Santi P. A., Wieslander J., Michael A. F. Distribution of familial nephritis antigen in normal tissue and renal basement membranes of patients with homozygous and heterozygous Alport familial nephritis. Relationship of familial nephritis and Goodpasture antigens to novel collagen chains and type IV collagen. Lab Invest. 1989 Sep;61(3):278–289. [PubMed] [Google Scholar]
  21. Kleppel M. M., Michael A. F., Fish A. J. Antibody specificity of human glomerular basement membrane type IV collagen NC1 subunits. Species variation in subunit composition. J Biol Chem. 1986 Dec 15;261(35):16547–16552. [PubMed] [Google Scholar]
  22. Martin G. R., Timpl R., Kühn K. Basement membrane proteins: molecular structure and function. Adv Protein Chem. 1988;39:1–50. doi: 10.1016/s0065-3233(08)60374-5. [DOI] [PubMed] [Google Scholar]
  23. Morrison K. E., Germino G. G., Reeders S. T. Use of the polymerase chain reaction to clone and sequence a cDNA encoding the bovine alpha 3 chain of type IV collagen. J Biol Chem. 1991 Jan 5;266(1):34–39. [PubMed] [Google Scholar]
  24. Muthukumaran G., Blumberg B., Kurkinen M. The complete primary structure for the alpha 1-chain of mouse collagen IV. Differential evolution of collagen IV domains. J Biol Chem. 1989 Apr 15;264(11):6310–6317. [PubMed] [Google Scholar]
  25. Myers J. C., Howard P. S., Jelen A. M., Dion A. S., Macarak E. J. Duplication of type IV collagen COOH-terminal repeats and species-specific expression of alpha 1(IV) and alpha 2(IV) collagen genes. J Biol Chem. 1987 Jul 5;262(19):9231–9238. [PubMed] [Google Scholar]
  26. Myers J. C., Jones T. A., Pohjolainen E. R., Kadri A. S., Goddard A. D., Sheer D., Solomon E., Pihlajaniemi T. Molecular cloning of alpha 5(IV) collagen and assignment of the gene to the region of the X chromosome containing the Alport syndrome locus. Am J Hum Genet. 1990 Jun;46(6):1024–1033. [PMC free article] [PubMed] [Google Scholar]
  27. Olson D. L., Anand S. K., Landing B. H., Heuser E., Grushkin C. M., Lieberman E. Diagnosis of hereditary nephritis by failure of glomeruli to bind anti-glomerular basement membrane antibodies. J Pediatr. 1980 Apr;96(4):697–699. doi: 10.1016/s0022-3476(80)80746-3. [DOI] [PubMed] [Google Scholar]
  28. Pihlajaniemi T., Pohjolainen E. R., Myers J. C. Complete primary structure of the triple-helical region and the carboxyl-terminal domain of a new type IV collagen chain, alpha 5(IV). J Biol Chem. 1990 Aug 15;265(23):13758–13766. [PubMed] [Google Scholar]
  29. Pihlajaniemi T., Tryggvason K., Myers J. C., Kurkinen M., Lebo R., Cheung M. C., Prockop D. J., Boyd C. D. cDNA clones coding for the pro-alpha1(IV) chain of human type IV procollagen reveal an unusual homology of amino acid sequences in two halves of the carboxyl-terminal domain. J Biol Chem. 1985 Jun 25;260(12):7681–7687. [PubMed] [Google Scholar]
  30. Pöschl E., Pollner R., Kühn K. The genes for the alpha 1(IV) and alpha 2(IV) chains of human basement membrane collagen type IV are arranged head-to-head and separated by a bidirectional promoter of unique structure. EMBO J. 1988 Sep;7(9):2687–2695. doi: 10.1002/j.1460-2075.1988.tb03122.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Saus J., Quinones S., MacKrell A., Blumberg B., Muthukumaran G., Pihlajaniemi T., Kurkinen M. The complete primary structure of mouse alpha 2(IV) collagen. Alignment with mouse alpha 1(IV) collagen. J Biol Chem. 1989 Apr 15;264(11):6318–6324. [PubMed] [Google Scholar]
  32. Saus J., Wieslander J., Langeveld J. P., Quinones S., Hudson B. G. Identification of the Goodpasture antigen as the alpha 3(IV) chain of collagen IV. J Biol Chem. 1988 Sep 15;263(26):13374–13380. [PubMed] [Google Scholar]
  33. Savage C. O., Noel L. H., Crutcher E., Price S. R., Grunfeld J. P., Lockwood C. M. Hereditary nephritis: immunoblotting studies of the glomerular basement membrane. Lab Invest. 1989 May;60(5):613–618. [PubMed] [Google Scholar]
  34. Savage C. O., Pusey C. D., Kershaw M. J., Cashman S. J., Harrison P., Hartley B., Turner D. R., Cameron J. S., Evans D. J., Lockwood C. M. The Goodpasture antigen in Alport's syndrome: studies with a monoclonal antibody. Kidney Int. 1986 Jul;30(1):107–112. doi: 10.1038/ki.1986.158. [DOI] [PubMed] [Google Scholar]
  35. Timpl R., Wiedemann H., van Delden V., Furthmayr H., Kühn K. A network model for the organization of type IV collagen molecules in basement membranes. Eur J Biochem. 1981 Nov;120(2):203–211. doi: 10.1111/j.1432-1033.1981.tb05690.x. [DOI] [PubMed] [Google Scholar]
  36. Wieslander J., Langeveld J., Butkowski R., Jodlowski M., Noelken M., Hudson B. G. Physical and immunochemical studies of the globular domain of type IV collagen. Cryptic properties of the Goodpasture antigen. J Biol Chem. 1985 Jul 15;260(14):8564–8570. [PubMed] [Google Scholar]
  37. Yang-Feng T. L., Floyd-Smith G., Nemer M., Drouin J., Francke U. The pronatriodilatin gene is located on the distal short arm of human chromosome 1 and on mouse chromosome 4. Am J Hum Genet. 1985 Nov;37(6):1117–1128. [PMC free article] [PubMed] [Google Scholar]
  38. Zhou J., Barker D. F., Hostikka S. L., Gregory M. C., Atkin C. L., Tryggvason K. Single base mutation in alpha 5(IV) collagen chain gene converting a conserved cysteine to serine in Alport syndrome. Genomics. 1991 Jan;9(1):10–18. doi: 10.1016/0888-7543(91)90215-z. [DOI] [PubMed] [Google Scholar]
  39. Zhou J., Hostikka S. L., Chow L. T., Tryggvason K. Characterization of the 3' half of the human type IV collagen alpha 5 gene that is affected in the Alport syndrome. Genomics. 1991 Jan;9(1):1–9. doi: 10.1016/0888-7543(91)90214-y. [DOI] [PubMed] [Google Scholar]

Articles from American Journal of Human Genetics are provided here courtesy of American Society of Human Genetics

RESOURCES