Skip to main content
Log in

The mouse Col2a-1 gene is highly conserved and is linked to Int-1 on Chromosome 15

  • Original Contributions
  • Published:
Mammalian Genome Aims and scope Submit manuscript

Abstract

Type II collagen is the major extracellular matrix component of cartilage and correct expression of the α1(II) collagen gene is important for vertebrate skeletal development. In order to provide the basis for studying the control of type II collagen gene expression in embryogenesis and in mouse models of human connective tissue disease, the complete mouse Col2-a1 gene has been isolated in a single cosmid clone, cosMcol.2, and partially characterized. The gene is approximately 30 kb and is highly conserved in exon/intron structure and nucleotide and amino acid sequence (>80% homology) when compared with the human, rat, bovine and chicken equivalents. A high degree of conservation was also found in the 5′ flanking region of the rat, human and mouse α1(II) collagen genes, including the presence of several G+C and C+T rich, direct repeat motifs. The sites of transcription start, termination codon and polyadenylation have also been identified. Unlike chicken, bovine and human, where polyA attachment is at a single site, for the mouse Col2a-1 gene two polyadenylation sites are utilized. Col2a-1 has also been localized by interspecies backcross analysis to the central portion of mouse Chromosome (Chr) 15, approximately 8 centiMorgans (cM) proximal of Int-1 and 18 cM distal of Myc. Col2a-1 is therefore included in a linkage group which is conserved on human Chr 12q.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Baldwin, C.T., Reginato, A.M., Smith, C., Jimenez, S.A. and Prockop, D.J.: Structure of cDNA clones coding for human type II procollagen: The α1(II) chain is more similar to the α1(I) chain than two other α chains of fibrillar collagens. Biochem J 262: 521–528, 1989.

    Google Scholar 

  • Benson-Chanda, V., Su, M.W., Weil, D., Chu, M.L. and Ramirez, F.: Cloning and analysis of the 5′ portion of the human type-III procollagen gene (COL3A1). Gene 78: 255–265, 1989.

    Google Scholar 

  • Benya, P.D. and Brown, P.D.: Modulation of the chondrocyte phenotype in vitro. In K.E. Kuetter, R. Schleyerbach and V.C. Hascall (eds.). Articular Cartilage Biochemistry, pp. 219–230, New York, Raven Press, 1986.

    Google Scholar 

  • Bornstein, P. and Sage, H.: Regulation of collagen gene expression. Prog Nucl Acids Res Mol Biol 37: 67–106, 1989.

    Google Scholar 

  • Cheah, K.S.E., Lau, E.T., Au, P.K.C. and Tam, P.P.L.: Expression of the mouse α1(II) collagen gene is not restricted to cartilage during development. Development, in press, 1991.

  • Cheah, K.S.E., Stoker, N.G., Griffin, J.R., Grosveld, F.G. and Solomon, E.: Identification and characterization of the human type II collagen gene (COL2A1). Proc Natl Acad Sci USA 82: 2555–2559, 1985.

    Google Scholar 

  • Chu, M.L. and Prockop, D.J.: Collagens: Gene structures. In P.M. Royce and B. Steinmann (eds.); Extracellular Matrix and Inheritable Disorders of Connective Tissue, Alan R. Liss, New York, in press, 1991.

    Google Scholar 

  • Cross, S.H. and Little, P.F.R.: A cosmid vector for systematic chromosome walking. Gene 49: 9–22, 1986.

    Google Scholar 

  • Davisson, M.T. and Roderick, T.H.: Linkage map. In M.F. Lyon and A.G. Searle (eds.); Genetic Variants and Strains of the Laboratory Mouse, Second Edition, pp. 416–427, Oxford University Press, Oxford, 1989.

    Google Scholar 

  • Devereux, J., Haeberli, P. and Smithies, O.: A comprehensive set of sequence analysis programs for the VAX. Nucl Acids Res 12: 387–395, 1984.

    Google Scholar 

  • Dion, A.S. and Myers, J.C.: COOH-terminal propeptides of the major human procollagens: Structural, functional and genetic comparisons. J Mol Biol 193: 127–143, 1987.

    Google Scholar 

  • Elima, K., Vuorio, T. and Vuorio, E.: Determination of the single polyadenylation site of the human pro-α1(II) collagen gene. Nucl Acids Res 15: 9499–9504, 1987.

    Google Scholar 

  • Francomano, C.A., Liberfarb, R., Hirose, T., Maumenee, I., Streeter, E., Meyers, D. and Pyeritz, R.E.: The Stickler syndrome: Evidence for close linkage to the structural gene of type II collagen. Genomics 1: 293–296, 1987.

    Google Scholar 

  • Grant, M.E., Ayad, S., Kwan, A.P.L., Bates, G.P., Thomas, J.T. and McClure, J.: The structure and synthesis of cartilage collagens. In A.M. Glauert (ed.); The Control of Tissue Damage, pp. 3–28, Amsterdam, Elsevier Press, 1988.

    Google Scholar 

  • Henikoff, S.: Unidirectional digestion with exonuclease III in DNA sequence analysis. Meths Enzymol 155: 156–165, 1987.

    Google Scholar 

  • Hermann, B. and Frischauf, A.-M.: Isolation of genomic DNA. Meths Enzymol 152: 180–183, 1987.

    Google Scholar 

  • Ireland, R.C., Kotarski, M.A., Johnston, L.A., Stadler, U., Birkenmeier, E. and Kozak, L.P.: Primary structure of the mouse glycerol-3-phosphate dehydrogenase gene. J Biol Chem 261: 11779–11785, 1986.

    Google Scholar 

  • Kohno, K., Sullivan, M. and Yamada, Y.: Structure of the promoter of the rat type II procollagen gene. J Biol Chem 260: 4441–4447, 1985.

    Google Scholar 

  • Kozak, L.P. and Birkenmeier, E.H.: Mouse sn-glycerol-3-phosphate dehydrogenase: Molecular cloning and genetic mapping of a cDNA sequence. Proc Natl Acad Sci USA 80: 3020–3024, 1983.

    Google Scholar 

  • Kozak, M.: An analysis of 5′-noncoding sequences from 699 vertebrate messenger RNAs. Nucl Acids Res 15: 8125–8148, 1987.

    Google Scholar 

  • Kuhn, K.: The classical collagens: Types I, II and III. In R. Mayne and R.E. Burgeson (eds.); Structure and Function of Collagen Types, pp. 1–42, Orlando, Academic Press, 1987.

    Google Scholar 

  • Lane, P.W. and Liu, H.M.: Association of megacolon with a new dominant spotting gene (Dom) in the mouse. J Hered 75: 435–439, 1984.

    Google Scholar 

  • Law, M.L., Tung, L., Morse, H.G., Berger, R., Jones, C., Cheah, K.S.E. and Solomon, E.: The human type II collagen gene (COL2A1) assigned to 12q14.3. Ann Hum Genet 50: 131–137, 1986.

    Google Scholar 

  • Lee, B., Vissing, H., Ramirez, F., Rogers, D. and Rimoin, D.: Identification of the molecular defect in a family with spondyloepiphyseal dysplasia. Science 244: 978–980, 1989.

    Google Scholar 

  • Lovell-Badge, R.H., Bygrave, A.E., Bradley, A., Robertson, E., Tilley, R. and Cheah, K.S.E.: Tissue-specific expression of the human type II collagen gene in mice. Proc Natl Acad Sci USA 84: 2803–2807, 1987.

    Google Scholar 

  • Lovell-Badge, R.H.: Introduction of DNA into embryonic stem cells. In E.J. Robertson (ed.); Teratocarcinomas and Embryonic Stem Cells—A Practical Approach, pp. 153–182, Oxford, IRL Press, 1987.

    Google Scholar 

  • Maniatis, T., Fritsch, E.F. and Sambrook, J.: Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratory Press, New York, 1982.

    Google Scholar 

  • Mayne, R. and Irwin, M.H.: Collagen types in cartilage. In K.E. Kuettner, R. Schleyerbach and V.C. Hascall (eds.); Articular Cartilage Biochemistry, pp. 23–35, New York, Raven Press, 1986.

    Google Scholar 

  • McLauchlan, J., Gaffney, D., Whitton, J.L. and Clements, J.B.: The consensus sequence YGTGTTYY located downstream from the AATAAA signal is required for efficient formation of mRNA 3′ termini. Nucl Acids Res 13: 1347–1368, 1985.

    Google Scholar 

  • Melton, D.A., Krieg, P.A., Rebagliati, M.R., Maniatis, T., Zinn, K. and Green, M.R.: Efficient in vitro synthesis of biologically active RNA and RNA hybridization probes from plasmids containing a bacteriphage SP6 promoter. Nucl Acids Res 12: 7035–7050, 1984.

    Google Scholar 

  • Meruelo, D., Rossomando, A., Scandalis, S., D'Eustachio, P., Fournier, R.E.K., Roop, D., Saxe, D., Blatt, C. and Nesbitt, M.N.: Assignment of the Ly-6-Ril-1-Sis-H-30-Pol-5/Xmv-72-Ins-3-Krt-1-Int-1-Gdc-1 region to mouse Chromosome 15. Immunogenetics 25: 361–372, 1987.

    Google Scholar 

  • Miller, E.J.: Isolation and characterization of a collagen from chick cartilage containing three identical alpha chains. Biochemistry 10: 1652–1659, 1971.

    Google Scholar 

  • Miller, E.J. and Gay, S.: The collagens: An overview and update. Meths Enzymol 144: 1–39, 1987.

    Google Scholar 

  • Nadeau, J., Grant, P. and Kosowsky, M.: Man on mouse homology map. Mouse Genome 87: 55–61, 1990.

    Google Scholar 

  • Ninomiya, Y., Showalter, A.M., Van der Rest, M., Seidah, N.G., Chretien, M. and Olsen, R.: Structure of the carboxylpropeptide of chicken type II procollagen determined by DNA and protein sequence analysis. Biochemistry 23: 617–624, 1984.

    Google Scholar 

  • Nunez, A.M., Kohno, K., Martin, G.R. and Yamada, Y.: Promoter region of the human pro-α1(II)-collagen gene. Gene 44: 11–16, 1986.

    Google Scholar 

  • Pearson, W.R. and Lipman, D.J.: Improved tools for biological sequence comparison. Proc Natl Acad Sci USA 85: 2444–2448, 1988.

    Google Scholar 

  • Ramirez, F., Bernard, M., Chu, M.L., Dickson, L., Sangiorgi, F., Weil, D., de Wet, W., Junien, C. and Sobel, M.: Isolation and characterization of the human fibrillar collagen genes. Ann NY Acad Sci 460: 117–129, 1985.

    Google Scholar 

  • Robert, B., Barton, P., Minty, A., Daubas, P., Weydert, A., Bonhomme, F., Catalan, J., Chazottes, D., Guénet, J.-L. and Buckingham, M.: Investigation of genetic linkage between myosin and actin genes using an interspecific backcross. Nature 314: 181–183, 1985.

    Google Scholar 

  • Rosenberg, L.C. and Buckwalter, J.A.: Cartilage proteoglycans. In K.E. Kuettner, R. Schleyerbach and V.C. Hascall (eds.); Articular Cartilage Biochemistry, pp. 39–54, New York, Raven Press, 1986.

    Google Scholar 

  • Ryan, M.C. and Sandell, L.J.: Differential expression of a cysteinerich domain in the amino-terminal propeptide of type II (cartilage) procollagen by alternative splicing of mRNA. J Biol Chem 265: 334–339, 1990.

    Google Scholar 

  • Ryan, M.C., Sieraski, M. and Sandell, L.: The human type II procollagen gene: Identification of an additional protein-coding domain and location of potential regulatory sequences in the promoter and first intron. Genomics 8: 41–48, 1990.

    Google Scholar 

  • Sakaguchi, A.Y., Lalley, P.A. and Naylor, S.L.: Human and mouse cellular Myc protooncogenes reside on chromosomes involved in numerical and structure aberrations in cancer. Somatic Cell Genet 9: 391–405, 1983.

    Google Scholar 

  • Sandell, L.J., Prentice, H.L., Kravis, D. and Upholt, W.B.: Structure and sequence of the chicken type II procollagen gene: Characterization of the region encoding the carboxyl-terminal telopeptide and propeptide. J Biol Chem 259: 7826–7834, 1984.

    Google Scholar 

  • Sanger, F., Nicklen, S. and Coulsen, A.R.: DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci USA 74: 5463–5467, 1977.

    Google Scholar 

  • Sangiorgi, F.O., Benson-Chanda, V., de Wet, W.J., Sobel, M.E. and Ramirez, F.: Analysis of cDNA and genomic clones coding for the pro-α1 chain of calf type II collagen. Nucl Acids Res 13: 2815–2826, 1985.

    Google Scholar 

  • Sangiorgi, F.O., Benson-Chanda, V., de Wet, W.J., Sobel, M.E., Tsipouras, P. and Ramirez, F.: Isolation and partial characterization of the entire human pro-α1(II) collagen gene. Nucl Acids Res 13: 2207–2225, 1985.

    Google Scholar 

  • Schwartzberg, P.L., Goff, S.P. and Robertson, E.J.: Germ-line transmission of a c-abl mutation produced by targeted gene disruption in ES cells. Science 246: 799–803, 1989.

    Google Scholar 

  • Shapiro, M.B. and Senapathy, P.: RNA splice junction of different classes of eukaryotes: Sequence statistics and functional implications in gene expression. Nucl Acids Res 15: 7155–7174, 1987.

    Google Scholar 

  • Stubbs, L., Huxley, C., Hogan, B., Evans, T., Fried, M., Duboule, D. and Lehrach, H.: The HOX-5 and Surfeit gene clusters are linked in the proximal portion of mouse Chromosome 2. Genomics 6: 645–650, 1990.

    Google Scholar 

  • Swalla, B.J., Upholt, W.B. and Solursh, M.: Analysis of type II collagen RNA localization in chick wing buds by in situ hybridization. Devl Biol 125: 51–58, 1988.

    Google Scholar 

  • Swimmer, C. and Shenk, T.: Selection of sequence elements that substitute for the standard AATAAA motif which signals 3′ processing and polyadenylation of late Simian virus 40 mRNAs. Nucl Acids Res 13: 8053–8063, 1985.

    Google Scholar 

  • Thomas, K.R., Folger, K.R. and Capecchi, M.R.: High frequency targeting of genes to specific sites in the mammalian genome. Cell 44: 419–428, 1986.

    Google Scholar 

  • Upholt, W.B. and Sandell, L.J.: Exon/intron organization of the chicken type II procollagen gene: Intron size distribution suggests a minimal intron size. Proc Natl Acad Sci USA 83: 2325–2329, 1986.

    Google Scholar 

  • Van-der-Meer-de-Jong, R., Dickinson, M.E., Woychik, R.P., Stubbs, L., Hetherington, C. and Hogan, B.L.: Location of the gene involving the small eye mutation on mouse Chromosome 2 suggests homology with human aniridia-2 (AN2). Genomics 7: 270–275, 1990.

    Google Scholar 

  • Veis, A.: Bones and teeth. In K.A. Piez and A.H. Reddi (eds.); Extracellular Matrix Biochemistry, pp. 329–374, New York, Elsevier Science Publishing Company, 1984.

    Google Scholar 

  • Vissing, H., D'Allessio, M., Lee, B., Ramirez, F., Godfrey, M. and Hollister, D.W.: Glycine serine substitution in the triple helical domain of pro-α1(II) collagen results in a lethal perinatal form of short-limbed dwarfism. J Biol Chem 264: 18265–18267, 1989.

    Google Scholar 

  • Von der Mark, K. and Von der Mark, H.: Immunological and biochemical studies of collagen type transition during in vitro chondrogenesis of chick limb mesodermal cells. J Cell Biol 73: 736–747, 1977.

    Google Scholar 

  • Vuorio, E. and de Crombrugghe, B.: The family of collagen genes. Ann Rev Biochem 59: 837–872, 1990.

    Google Scholar 

  • Waley, R.B., Little, P.F.R., Pritchard, J. and Cowell, J.K.: Isolation and regional localization of DNA sequences from a human chromosome 11-specific cosmid library. Hum Genet 84: 417–423, 1990.

    Google Scholar 

  • Wickens, M.: How the messenger got its tail: Addition of poly(A) in the nucleus. Trends Biochem Sci 15: 277–281, 1990.

    Google Scholar 

  • Wickens, M.: In the beginning is the end: Regulation of poly(A) addition and removal during early development. Trends Biochem Sci 15: 320–324, 1990.

    Google Scholar 

  • Wilkinson, D.G., Bailes, J.A. and McMahon, A.P.: Expression of the protooncogene Int-1 is restricted to specific neural cells in the developing mouse embryo. Cell 50: 79–88, 1987.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

The sequence data presented in this paper have been submitted to GenBank and have been assigned the accession numbers M63708, M63709 and M63710.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Cheah, K.S.E., Au, P.K.C., Lau, E.T. et al. The mouse Col2a-1 gene is highly conserved and is linked to Int-1 on Chromosome 15. Mammalian Genome 1, 171–183 (1991). https://doi.org/10.1007/BF00351064

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00351064

Keywords

Navigation