Summary
Fibroblasts derived from a skin biopsy of a patient with the Ehlers-Danlos syndrome (EDS) type IV were cultured in monolayer. The amount of collagen synthesized during a 24-h pulse was not different from that found with normal fibroblasts. Chromatographic procedures and immunofluorescence staining showed a normal synthesis of type I procollagen and collagen but a deficiency in synthesis of type III procollagen and collagen. This could be corroborated by radioimmuno assays showing a reduction in type III procollagen by about 90%. The secretion and degradation of collagens was not altered. The results demonstrate that the molecular defect in this particular patient is due to an impairment of the mechanism controlling the gene expression for type III procollagen.
Zusammenfassung
Von einem Patienten mit den klinischen Symptomen eines Ehlers-Danlos-Syndroms Typ IV wurden Fibroblastenkulturen gezüchtet. Diese synthetisierten dieselbe Menge an Kollagen wie Kontroll-Fibroblasten und zeigten auch ein identisches Sekretions-und Degradations-Verhalten. Biochemische und immunochemische Methoden wiesen jedoch eine signifikante Reduktion des Anteils von Typ III-Kollagen auf etwa 10% des Normalwertes auf.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Abbreviations
- BAPN:
-
β-aminopropionitrile
- CM:
-
carboxy-methyl
- DEAE:
-
diethylaminoethyl
- EDS:
-
Ehlers-Danlos syndrome
- EDTA:
-
ethylendiaminetetracetate
- S.C.:
-
subcutaneous
References
Miller EJ (1976) Biochemical characteristics and biological significance of the genetically distinct collagens. Mol Cell Biochem 13:165–182
Harwood R (1979) Collagen polymorphism and messenger RNA. Int Rev Connect Tissue Res 8:159–226
Prockop DJ, Kivirriko KI, Tuderman L, Guzman NA (1979) The biosynthesis of collagen and its disorders. N Engl J Med 301:13–23; 77–85
McKusick VA (1972) Heritable disorders of connective tissue 4th ed. Mosby, St. Louis
Hollister DW (1978) Heritable disorders of connective tissue: Ehlers-Danlos syndrome. Pediatr Clin North Am 23:575–591
Diferrante N, Leachman RD, Angelini P, Donnelly PV, Francis Almazon A (1975) Lysyl oxidase deficiency in Ehlers-Danlos syndrome type V. Connect Tissue Res 3:49–54
Pinnel SR, Krane SM, Kenzora JE, Glimcher MJ (1972) A heritable disorder of connective tissue hydroxy lysine-deficient collagen disease. N Engl J Med 286:1013–1020
Lichstenstein JR, Martin GR, Kohn LD, Byers PH, McKusick VA (1973) Defect in conversion of procollagen to collagen in a form of Ehlers-Danlos syndrome. Science 182:298–300
Pope FM, Martin GR, Lichstenstein JR, Penttinen R, Gerson B, Rowe DW, McKusick VA (1975) Patients with the Ehlers-Danlos syndrome type IV lack type III collagen. Proc Natl Acad Sci USA 72:1314–1316
Barabas AP (1967) Heterogeneity of the Ehlers-Danlos syndrome: Description of three clinical types and a hypothesis to explain basic defect(s). Br Med J 2:612–613
Gay S, Martin GR, Müller PK, Timpl R, Kühn K (1976) Simultaneous synthesis of types I and III collagen by fibroblasts in culture. Proc Natl Acad Sci USA 73:4037–4040
Byers PH, Holbrook KA, McGillivray B, McLeod PM, Lowry RB (1979) Clinical and ultrastructural heterogeneity of type IV Ehlers-Danlos syndrome. Human Genet 47:141–150
Byers PH, Holbrook KA, Smith LT, Bornstein P, McGillivray B, McLeod PM (1978) Altered secretion of type III collagen in a form of type IV Ehlers-Danlos syndrome. Clin Res 26:512A
Krieg T, Hörlein D, Wiestner M, Müller PK (1978) Aminoterminal extension peptides from type I procollagen normalize excessive collagen synthesis of scleroderma fibroblasts. Arch Dermatol Res 263:171–180
Smith BD, Byers PH, Martin GR (1972) Production of procollagen by human fibroblasts in culture. Proc Natl Acad Sci USA 69:3260–3262
Piez KA, Eigner EA, Lewis MS (1963) The chromatographic separation and amino-acid composition of subunits of several collagens. Biochemistry 2:58–66
Pontz BF, Müller PK, Meigel WN (1973) A study of the conversion of procollagen. Release and recovery of procollagen peptide in the culture medium. J Biol Chem 248:7558–7564
Piez KA (1968) Molecular weight determination of random coil polypeptides from collagen by molecular sieve chromatography. Anal Biochem 26:305–312
Rohde H, Vargas L, Hahn E, Kalbfleisch H, Bruguera M, Timpl R (1979) Radioimmunoassay for type III procollagen peptide and its application to human liver disease. Eur J Clin Invest 9:451–459
Timpl R, Wick G, Gay S (1977) Antibodies to distinct types of collagens and procollagens and their application in immunohistology. J Immunol Methods 18:165–182
Krieg T, Aumailley M, Dessau W, Wiestner M, Müller PK (1980) Synthesis of collagen by human fibroblasts and their SV 40 transformants. Exp Cell Res 125:23–30
Nowack H, Gay S, Wick G, Becker U, Timpl R (1976) Preparation and use in immunohistology of antibodies specific for type I and type III collagen and procollagen. J Immunol Methods 12:117–124
Beigthon P (1970) The Ehlers-Danlos syndrome. Heinemann, London
Pope FM, Martin GR, McKusick VA (1977) Inheritance of Ehlers-Danlos syndrome type IV. J Med Genet 14:200–204
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Aumailley, M., Krieg, T., Dessau, W. et al. Biochemical and immunological studies of fibroblasts derived from a patient with Ehlers-Danlos Syndrome Type IV. Arch Dermatol Res 269, 169–177 (1980). https://doi.org/10.1007/BF00406537
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF00406537