Cell and Tissue Research

, Volume 319, Issue 2, pp 279–287 | Cite as

Transplantation of reconstructed human skin on nude mice: a model system to study expression of human tenascin-X and elastic fiber components

  • Manon C. Zweers
  • Joost Schalkwijk
  • Toin H. van Kuppevelt
  • Ivonne M. van Vlijmen-Willems
  • Mieke Bergers
  • Claire Lethias
  • Evert N. Lamme
Regular Article

Abstract

Tenascin-X is a large extracellular matrix protein that is widely expressed in connective tissues during development and in the adult. Genetically determined deficiency of tenascin-X causes the connective tissue disease Ehlers–Danlos syndrome. These patients show reduced collagen density and fragmentation of elastic fibers in their skin. In vitro studies on the role of tenascin-X in elastic fiber biology are hampered because monolayers of fibroblasts do not deposit tenascin-X and elastic fibers into the extracellular matrix. Here, we applied an organotypic culture model of fibroblasts and keratinocytes to address this issue. We investigated the deposition of tenascin-X and elastin into skin-equivalent in vitro and also in vivo after transplantation onto immunodeficient mice. Whereas tenascin-C and fibrillin-1 were readily expressed in the skin-equivalents before transplantation, tenascin-X and elastin were not present. Three weeks post-grafting, a network of elastin was observed that coincided with the appearance of tenascin-X. At the ultrastructural level, microfibrils were observed, some of which were associated with elastin. Transplanted skin-equivalents containing tenascin-X-deficient fibroblasts showed deposition of immunoreactive elastin in similar quantities and distribution as those containing control fibroblasts. This suggests that tenascin-X is important for the stability and maintenance of established elastin fibers, rather than for the initial phase of elastogenesis. Thus, the transplantation of reconstructed skin on nude mice allows the study of tenascin-X and elastin expression and could be used as a model system to study the potential role of tenascin-X in matrix assembly and stability.

Keywords

Tenascin-X Connective tissue Organotypic culture Skin-equivalent Transplantation Human Mouse (male athymic nude BALB/c) 

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Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Manon C. Zweers
    • 1
  • Joost Schalkwijk
    • 1
  • Toin H. van Kuppevelt
    • 2
  • Ivonne M. van Vlijmen-Willems
    • 1
  • Mieke Bergers
    • 1
  • Claire Lethias
    • 3
  • Evert N. Lamme
    • 1
  1. 1.Department of DermatologyUniversity Medical Centre NijmegenNijmegenThe Netherlands
  2. 2.Department of BiochemistryUniversity Medical Centre NijmegenNijmegenThe Netherlands
  3. 3.Institut de Biologie et Chimie des ProteinesCNRSLyonFrance

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