Search tips
Search criteria 


Logo of molmedLink to Publisher's site
Mol Med. 1997 October; 3(10): 654–662.
PMCID: PMC2230233

Altered procollagen mRNA expression during the progression of avian scleroderma.


BACKGROUND: Spontaneous animal models of human autoimmune diseases provide the means to study the very first pathogenetic events, which is not possible in their human counterparts. This is particularly true for connective tissue diseases in which clinical symptoms become manifest only after a long and still obscure course of immunologic, inflammatory, and fibrotic processes. University of California at Davis line 200 chickens (UCD-200) develop a hereditary scleroderma-like disease resembling the entire spectrum of human systemic sclerosis, such as early endothelial cell damage, severe lymphocytic infiltration, and accumulation of collagen in skin and internal organs. MATERIALS AND METHODS: In the present study, we investigated mRNA levels of alpha 1(I), alpha 2(I), alpha 1(II), alpha 1(III), alpha 1(VI), alpha 2(VI), and alpha 3(VI) procollagen and GAPDH using digoxigenin-labeled antisense probes in a nonradioactive ribonuclease protection assay (RPA). We analyzed tissue samples from comb, esophagus, heart, lung, and liver of UCD-200 chickens at different stages of the disease, and healthy UCD-058 chickens. RESULTS: During the early inflammatory stage of the disease, the ratios of procollagen types VI/I and types VI/III increased 7-fold in comb tissue, followed by a 3-fold elevation in type I procollagen transcripts in the late acute stage. In the chronic stage, alpha 1(III) procollagen message was increased 2-fold. Additionally, hybridization with the 180 bp alpha 2(I) antisense probe resulted in two bands of 180 bp and 115 bp, respectively, in the RPA. The ratio of these two previously undescribed bands changes in the early stage of the disease both in comb and esophagus. CONCLUSIONS: In an animal model with a spontaneous scleroderma-like disease we found a characteristic, sequential increase in type VI, type I, and type III procollagen transcripts, and we found evidence for the presence and altered ratio of two mRNA variants of alpha 2(I) procollagen, possibly caused by alternative splicing. Comparative analysis of alpha 2(I) procollagen variants in early stages of avian scleroderma and human SSc might provide answers to unresolved questions concerning the molecular basis for generalized fibrosis in scleroderma.

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 (2.1M), 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.
  • Jimenez SA, Williams CJ, Myers JC, Bashey RI. Increased collagen biosynthesis and increased expression of type I and type III procollagen genes in tight skin (TSK) mouse fibroblasts. J Biol Chem. 1986 Jan 15;261(2):657–662. [PubMed]
  • Bocchieri MH, Henriksen PD, Kasturi KN, Muryoi T, Bona CA, Jimenez SA. Evidence for autoimmunity in the tight skin mouse model of systemic sclerosis. Arthritis Rheum. 1991 May;34(5):599–605. [PubMed]
  • Gershwin ME, Abplanalp H, Castles JJ, Ikeda RM, van der Water J, Eklund J, Haynes D. Characterization of a spontaneous disease of white leghorn chickens resembling progressive systemic sclerosis (scleroderma). J Exp Med. 1981 Jun 1;153(6):1640–1659. [PMC free article] [PubMed]
  • Van de Water J, Boyd R, Wick G, Gershwin ME. The immunologic and genetic basis of avian scleroderma, an inherited fibrotic disease of line 200 chickens. Int Rev Immunol. 1994;11(3):273–282. [PubMed]
  • van de Water J, Gershwin ME, Abplanalp H, Wick G, von der Mark K. Serial observations and definition of mononuclear cell infiltrates in avian scleroderma, an inherited fibrotic disease of chickens. Arthritis Rheum. 1984 Jul;27(7):807–815. [PubMed]
  • van de Water J, Haapanen L, Boyd R, Abplanalp H, Gershwin ME. Identification of T cells in early dermal lymphocytic infiltrates in avian scleroderma. Arthritis Rheum. 1989 Aug;32(8):1031–1040. [PubMed]
  • Gruschwitz MS, Moormann S, Krömer G, Sgonc R, Dietrich H, Boeck G, Gershwin ME, Boyd R, Wick G. Phenotypic analysis of skin infiltrates in comparison with peripheral blood lymphocytes, spleen cells and thymocytes in early avian scleroderma. J Autoimmun. 1991 Aug;4(4):577–593. [PubMed]
  • Sgonc R, Gruschwitz MS, Dietrich H, Recheis H, Gershwin ME, Wick G. Endothelial cell apoptosis is a primary pathogenetic event underlying skin lesions in avian and human scleroderma. J Clin Invest. 1996 Aug 1;98(3):785–792. [PMC free article] [PubMed]
  • Haynes DC, Gershwin ME. Diversity of autoantibodies in avian scleroderma. An inherited fibrotic disease of White Leghorn chickens. J Clin Invest. 1984 Jun;73(6):1557–1568. [PMC free article] [PubMed]
  • Gruschwitz MS, Shoenfeld Y, Krupp M, Gershwin ME, Penner E, Brezinschek HP, Wick G. Antinuclear antibody profile in UCD line 200 chickens: a model for progressive systemic sclerosis. Int Arch Allergy Immunol. 1993;100(4):307–313. [PubMed]
  • LeRoy EC. The connective tissue in scleroderma. Coll Relat Res. 1981 Apr;1(3):301–308. [PubMed]
  • Duncan MR, Wilson TJ, Van De Water J, Berman B, Boyd R, Wick G, Gershwin ME. Cultured fibroblasts in avian scleroderma, an autoimmune fibrotic disease, display an activated phenotype. J Autoimmun. 1992 Oct;5(5):603–615. [PubMed]
  • Kähäri VM, Sandberg M, Kalimo H, Vuorio T, Vuorio E. Identification of fibroblasts responsible for increased collagen production in localized scleroderma by in situ hybridization. J Invest Dermatol. 1988 May;90(5):664–670. [PubMed]
  • Abplanalp H, Gershwin ME, Johnston E, Reid J. Genetic control of avian scleroderma. Immunogenetics. 1990;31(5-6):291–295. [PubMed]
  • Mäkelä JK, Vuorio E. Type I collagen messenger RNA levels in experimental granulation tissue and silicosis in rats. Med Biol. 1986;64(1):15–22. [PubMed]
  • Vuorio E, Sandell L, Kravis D, Sheffield VC, Vuorio T, Dorfman A, Upholt WB. Construction and partial characterization of two recombinant cDNA clones for procollagen from chicken cartilage. Nucleic Acids Res. 1982 Feb 25;10(4):1175–1192. [PMC free article] [PubMed]
  • Yamada Y, Kühn K, de Crombrugghe B. A conserved nucleotide sequence, coding for a segment of the C-propeptide, is found at the same location in different collagen genes. Nucleic Acids Res. 1983 May 11;11(9):2733–2744. [PMC free article] [PubMed]
  • Bonaldo P, Russo V, Bucciotti F, Bressan GM, Colombatti A. Alpha 1 chain of chick type VI collagen. The complete cDNA sequence reveals a hybrid molecule made of one short collagen and three von Willebrand factor type A-like domains. J Biol Chem. 1989 Apr 5;264(10):5575–5580. [PubMed]
  • Trüeb B, Schaeren-Wiemers N, Schreier T, Winterhalter KH. Molecular cloning of chicken type VI collagen. Primary structure of the subunit alpha 2(VI)-pepsin. J Biol Chem. 1989 Jan 5;264(1):136–140. [PubMed]
  • Bonaldo P, Russo V, Bucciotti F, Doliana R, Colombatti A. Structural and functional features of the alpha 3 chain indicate a bridging role for chicken collagen VI in connective tissues. Biochemistry. 1990 Feb 6;29(5):1245–1254. [PubMed]
  • Dugaiczyk A, Haron JA, Stone EM, Dennison OE, Rothblum KN, Schwartz RJ. Cloning and sequencing of a deoxyribonucleic acid copy of glyceraldehyde-3-phosphate dehydrogenase messenger ribonucleic acid isolated from chicken muscle. Biochemistry. 1983 Mar 29;22(7):1605–1613. [PubMed]
  • Mays PK, Bishop JE, Laurent GJ. Age-related changes in the proportion of types I and III collagen. Mech Ageing Dev. 1988 Nov 30;45(3):203–212. [PubMed]
  • Heckmann M, Aumailley M, Hatamochi A, Chu ML, Timpl R, Krieg T. Down-regulation of alpha 3(VI) chain expression by gamma-interferon decreases synthesis and deposition of collagen type VI. Eur J Biochem. 1989 Jul 1;182(3):719–726. [PubMed]
  • Koller E, Trueb B. Characterization of the chicken alpha 1(VI) collagen promoter. Eur J Biochem. 1992 Sep 15;208(3):769–774. [PubMed]
  • Botstein GR, Sherer GK, Leroy EC. Fibroblast selection in scleroderma. An alternative model of fibrosis. Arthritis Rheum. 1982 Feb;25(2):189–195. [PubMed]
  • Kähäri VM. Activation of dermal connective tissue in scleroderma. Ann Med. 1993 Dec;25(6):511–518. [PubMed]
  • Scharffetter K, Lankat-Buttgereit B, Krieg T. Localization of collagen mRNA in normal and scleroderma skin by in-situ hybridization. Eur J Clin Invest. 1988 Feb;18(1):9–17. [PubMed]
  • Perlish JS, Lemlich G, Fleischmajer R. Identification of collagen fibrils in scleroderma skin. J Invest Dermatol. 1988 Jan;90(1):48–54. [PubMed]
  • Kähäri VM, Heino J, Vuorio E. Interleukin-1 increases collagen production and mRNA levels in cultured skin fibroblasts. Biochim Biophys Acta. 1987 Jul 6;929(2):142–147. [PubMed]
  • Myers RM, Larin Z, Maniatis T. Detection of single base substitutions by ribonuclease cleavage at mismatches in RNA:DNA duplexes. Science. 1985 Dec 13;230(4731):1242–1246. [PubMed]

Articles from Molecular Medicine are provided here courtesy of The Feinstein Institute for Medical Research at North Shore LIJ