Expression of the Collagen VI alpha 5 and alpha 6 Chains in Normal Human Skin and in Skin of Patients with Collagen VI-Related Myopathies

Collagen VI is an extracellular matrix protein with critical roles in maintaining muscle and skin integrity and function. Skin abnormalities, including predisposition to keratosis pilaris and abnormal scarring, were described in Ullrich congenital muscular dystrophy (UCMD) and Bethlem myopathy (BM) patients carrying mutations in COL6A1, COL6A2, and COL6A3 genes, whereas COL6A5, previously designated as COL29A1, was linked to atopic dermatitis. To gain insight into the function of the newly identified collagen VI alpha 5 and alpha 6 chains in human skin, we studied their expression and localization in normal subjects and in genetically characterized UCMD and BM patients. We found that localization of alpha 5, and to a lesser extent alpha 6, is restricted to the papillary dermis, where the protein mainly colocalizes with collagen fibrils. In addition, both chains were found around blood vessels. In UCMD patients with COL6A1 or COL6A2 mutations, immunolabeling for alpha 5 and alpha 6 was often altered, whereas in a UCMD and in a BM patient, each with a COL6A3 mutation, expression of alpha 5 and alpha 6 was apparently unaffected, suggesting that these chains may substitute for alpha 3, forming alpha 1 alpha 2 alpha 5 or alpha 1 alpha 2 alpha 6 heterotrimers.