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. 1998 May;4(5):356–360.

Effect of targeted mutation in collagen V alpha 2 gene on development of cutaneous hyperplasia in tight skin mice.

R G Phelps 1, C Murai 1, S Saito 1, A Hatakeyama 1, K Andrikopoulos 1, K N Kasturi 1, C A Bona 1
PMCID: PMC2230382  PMID: 9642685

Abstract

Collagen V plays a major regulatory role in the formation of heterotypic fibers of the dermis and cartilaginous tissues as well as in the assembly of extracellular matrix. The pN/pN mouse, which is defective in collagen V alpha 2 gene, exhibits skeletal abnormalities, skin fragility, and alterations in the collagen fiber organization, whereas the TSK/+ mouse, which is defective in fibrillin-1, the major component of microfibrils present in the extracellular matrix, develops cutaneous hyperplasia and autoimmunity. We have studied the role of collagen V in the formation of heterotypic collagen fibers in F1 mice, which are obtained by breeding pN/pN with TSK/+ mice. Our results show that F1 progeny neither develop cutaneous hyperplasia nor produce anti-topoisomerase I autoantibodies, unlike TSK/+ mice. The diameter of the collagen fibrils in the skin is also comparable to that found in control mice. Thus, the phenotypic changes observed in the TSK mouse could be reversed by genetic complementation with a collagen V-defective mouse.

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Selected References

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

  1. Andrikopoulos K., Liu X., Keene D. R., Jaenisch R., Ramirez F. Targeted mutation in the col5a2 gene reveals a regulatory role for type V collagen during matrix assembly. Nat Genet. 1995 Jan;9(1):31–36. doi: 10.1038/ng0195-31. [DOI] [PubMed] [Google Scholar]
  2. Birk D. E., Fitch J. M., Babiarz J. P., Doane K. J., Linsenmayer T. F. Collagen fibrillogenesis in vitro: interaction of types I and V collagen regulates fibril diameter. J Cell Sci. 1990 Apr;95(Pt 4):649–657. doi: 10.1242/jcs.95.4.649. [DOI] [PubMed] [Google Scholar]
  3. Green M. C., Sweet H. O., Bunker L. E. Tight-skin, a new mutation of the mouse causing excessive growth of connective tissue and skeleton. Am J Pathol. 1976 Mar;82(3):493–512. [PMC free article] [PubMed] [Google Scholar]
  4. Hatakeyama A., Kasturi K. N., Wolf I., Phelps R. G., Bona C. A. Correlation between the concentration of serum anti-topoisomerase I autoantibodies and histological and biochemical alterations in the skin of tight skin mice. Cell Immunol. 1996 Jan 10;167(1):135–140. doi: 10.1006/cimm.1996.0017. [DOI] [PubMed] [Google Scholar]
  5. Jimenez S. A., Williams C. J., Myers J. C., Bashey R. I. 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] [Google Scholar]
  6. Kasturi K. N., Hatakeyama A., Murai C., Gordon R., Phelps R. G., Bona C. A. B-cell deficiency does not abrogate development of cutaneous hyperplasia in mice inheriting the defective fibrillin-1 gene. J Autoimmun. 1997 Dec;10(6):505–517. doi: 10.1006/jaut.1997.0158. [DOI] [PubMed] [Google Scholar]
  7. Kivirikko K. I. Collagens and their abnormalities in a wide spectrum of diseases. Ann Med. 1993 Apr;25(2):113–126. doi: 10.3109/07853899309164153. [DOI] [PubMed] [Google Scholar]
  8. Laird P. W., Zijderveld A., Linders K., Rudnicki M. A., Jaenisch R., Berns A. Simplified mammalian DNA isolation procedure. Nucleic Acids Res. 1991 Aug 11;19(15):4293–4293. doi: 10.1093/nar/19.15.4293. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Muryoi T., Kasturi K. N., Kafina M. J., Cram D. S., Harrison L. C., Sasaki T., Bona C. A. Antitopoisomerase I monoclonal autoantibodies from scleroderma patients and tight skin mouse interact with similar epitopes. J Exp Med. 1992 Apr 1;175(4):1103–1109. doi: 10.1084/jem.175.4.1103. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Muryoi T., Kasturi K. N., Kafina M. J., Saitoh Y., Usuba O., Perlish J. S., Fleischmajer R., Bona C. A. Self reactive repertoire of tight skin mouse: immunochemical and molecular characterization of anti-topoisomerase I autoantibodies. Autoimmunity. 1991;9(2):109–117. doi: 10.3109/08916939109006746. [DOI] [PubMed] [Google Scholar]
  11. Nicholls A. C., Oliver J. E., McCarron S., Harrison J. B., Greenspan D. S., Pope F. M. An exon skipping mutation of a type V collagen gene (COL5A1) in Ehlers-Danlos syndrome. J Med Genet. 1996 Nov;33(11):940–946. doi: 10.1136/jmg.33.11.940. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Osborn T. G., Bashey R. I., Moore T. L., Fischer V. W. Collagenous abnormalities in the heart of the tight-skin mouse. J Mol Cell Cardiol. 1987 Jun;19(6):581–587. doi: 10.1016/s0022-2828(87)80363-2. [DOI] [PubMed] [Google Scholar]
  13. Osborn T. G., Bauer N. E., Ross S. C., Moore T. L., Zuckner J. The tight-skin mouse: physical and biochemical properties of the skin. J Rheumatol. 1983 Oct;10(5):793–796. [PubMed] [Google Scholar]
  14. Phelps R. G., Daian C., Shibata S., Fleischmajer R., Bona C. A. Induction of skin fibrosis and autoantibodies by infusion of immunocompetent cells from tight skin mice into C57BL/6 Pa/Pa mice. J Autoimmun. 1993 Dec;6(6):701–718. doi: 10.1006/jaut.1993.1059. [DOI] [PubMed] [Google Scholar]
  15. Shero J. H., Bordwell B., Rothfield N. F., Earnshaw W. C. High titers of autoantibodies to topoisomerase I (Scl-70) in sera from scleroderma patients. Science. 1986 Feb 14;231(4739):737–740. doi: 10.1126/science.3003910. [DOI] [PubMed] [Google Scholar]
  16. Siracusa L. D., McGrath R., Ma Q., Moskow J. J., Manne J., Christner P. J., Buchberg A. M., Jimenez S. A. A tandem duplication within the fibrillin 1 gene is associated with the mouse tight skin mutation. Genome Res. 1996 Apr;6(4):300–313. doi: 10.1101/gr.6.4.300. [DOI] [PubMed] [Google Scholar]
  17. Szapiel S. V., Fulmer J. D., Hunninghake G. W., Elson N. A., Kawanami O., Ferrans V. J., Crystal R. G. Hereditary emphysema in the tight-skin (Tsk/+) mouse. Am Rev Respir Dis. 1981 Jun;123(6):680–685. doi: 10.1164/arrd.1981.123.6.680. [DOI] [PubMed] [Google Scholar]
  18. Vogel A., Holbrook K. A., Steinmann B., Gitzelmann R., Byers P. H. Abnormal collagen fibril structure in the gravis form (type I) of Ehlers-Danlos syndrome. Lab Invest. 1979 Feb;40(2):201–206. [PubMed] [Google Scholar]

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