title: 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.
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.
authors.affiliation: Center for Biochemistry, Medical Faculty, University of Cologne, Cologne, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Lettmann
authors.affiliation: Institute of Cardiovascular Research and Sport Medicine, German Sport University, Cologne, Germany.
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Bloch
authors.affiliation: Center for Biochemistry, Medical Faculty, University of Cologne, Cologne, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Maaß
authors.affiliation: Institute of Biomechanics and Orthopaedics, German Sport University, Cologne, Germany; Cologne Center for Musculoskeletal Biomechanics, Medical Faculty, University of Cologne, Cologne, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Niehoff
authors.affiliation: Department of Dermatology, University of Cologne, Cologne, Germany.
authors.forename: Jan-Niklas
authors.initials: JN
authors.lastname: Schulz
authors.affiliation: Department of Dermatology, University of Cologne, Cologne, Germany.
authors.forename: Beate
authors.initials: B
authors.lastname: Eckes
authors.affiliation: 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.
authors.forename: Sabine A
authors.initials: SA
authors.lastname: Eming
authors.affiliation: Department of Molecular Medicine, University of Padova, Padova, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Bonaldo
authors.affiliation: 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.
authors.forename: Mats
authors.initials: M
authors.lastname: Paulsson
authors.affiliation: Center for Biochemistry, Medical Faculty, University of Cologne, Cologne, Germany; Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany.
authors.forename: Raimund
authors.initials: R
authors.lastname: Wagener
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D024142:Collagen Type VI / Q000032:analysis / Q000235:genetics* / Q000648:ultrastructure; D004195:Disease Models, Animal; D005260:Female; D017353:Gene Deletion; D005786:Gene Expression Regulation; D051379:Mice; D008810:Mice, Inbred C57BL; D009135:Muscular Diseases / Q000235:genetics* / Q000473:pathology*; D012867:Skin / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure*; D013718:Tensile Strength; D014945:Wound Healing
chemical_list: C540085:Col6a1 protein, mouse; D024142:Collagen Type VI