Col6a1 null mice as a model to study skin phenotypes in patients with collagen VI related myopathies: expression of classical and novel collagen VI variants during wound healing

Sandra Lettmann; Wilhelm Bloch; Tobias Maaß; Anja Niehoff; Jan-Niklas Schulz; Beate Eckes; Sabine A Eming; Paolo Bonaldo; Mats Paulsson; Raimund Wagener

doi:10.1371/journal.pone.0105686

Col6a1 null mice as a model to study skin phenotypes in patients with collagen VI related myopathies: expression of classical and novel collagen VI variants during wound healing

PLoS One. 2014 Aug 26;9(8):e105686. doi: 10.1371/journal.pone.0105686. eCollection 2014.

Authors

Affiliations

¹ Center for Biochemistry, Medical Faculty, University of Cologne, Cologne, Germany.
² Institute of Cardiovascular Research and Sport Medicine, German Sport University, Cologne, Germany.
³ Institute of Biomechanics and Orthopaedics, German Sport University, Cologne, Germany; Cologne Center for Musculoskeletal Biomechanics, Medical Faculty, University of Cologne, Cologne, Germany.
⁴ Department of Dermatology, University of Cologne, Cologne, Germany.
⁵ Department of Dermatology, University of Cologne, Cologne, Germany; Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, Cologne, Germany.
⁶ Department of Molecular Medicine, University of Padova, Padova, Italy.
⁷ Center for Biochemistry, Medical Faculty, University of Cologne, Cologne, Germany; Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, Cologne, Germany.
⁸ Center for Biochemistry, Medical Faculty, University of Cologne, Cologne, Germany; Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany.

Abstract

Patients suffering from collagen VI related myopathies caused by mutations in COL6A1, COL6A2 and COL6A3 often also display skin abnormalities, like formation of keloids or "cigarette paper" scars, dry skin, striae rubrae and keratosis pilaris (follicular keratosis). Here we evaluated if Col6a1 null mice, an established animal model for the muscle changes in collagen VI related myopathies, are also suitable for the study of mechanisms leading to the skin pathology. We performed a comprehensive study of the expression of all six collagen VI chains in unwounded and challenged skin of wild type and Col6a1 null mice. Expression of collagen VI chains is regulated in both skin wounds and bleomycin-induced fibrosis and the collagen VI α3 chain is proteolytically processed in both wild type and Col6a1 null mice. Interestingly, we detected a decreased tensile strength of the skin and an altered collagen fibril and basement membrane architecture in Col6a1 null mice, the latter being features that are also found in collagen VI myopathy patients. Although Col6a1 null mice do not display an overt wound healing defect, these mice are a relevant animal model to study the skin pathology in collagen VI related disease.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cells, Cultured
Collagen Type VI / analysis
Collagen Type VI / genetics*
Collagen Type VI / ultrastructure
Disease Models, Animal
Female
Gene Deletion
Gene Expression Regulation
Mice
Mice, Inbred C57BL
Muscular Diseases / genetics*
Muscular Diseases / pathology*
Skin / metabolism
Skin / pathology*
Skin / ultrastructure*
Tensile Strength
Wound Healing*

Substances

Col6a1 protein, mouse
Collagen Type VI

Grants and funding

The work was funded to WB, BE, SAE, MP and RW by the Collaborative Research Centre (SFB) 829 “Molecular Mechanisms regulating Skin Homeostasis”, an interdisciplinary research centre of excellence funded by the Deutsche Forschungsgemeinschaft (DFG). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.