In addition to the obvious muscular phenotype many patients also display skin abnormalities, including a predisposition for keratosis pilaris, abnormal scarring with formation of keloids or ����cigarette paper���� scars, dry skin, and striae rubrae. Collagen VI forms a distinct microfibrillar network in most forms of extracellular matrix that anchors interstitial structures, such as nerves, blood vessels and larger collagen fibrils. In addition to being a collagen it belongs to the superfamily of proteins containing von Willebrand factor A domains, globular protein modules that act by mediating protein-protein interactions. Collagen VI was long considered to consist of three genetically distinct a-chains. These chains form heterotrimeric monomers that assemble into dimers and tetramers already in the cell. After secretion, polymers are formed by end-to-end interactions of the pre-assembled tetramers, yielding the characteristic beaded filaments seen by electron microscopy. More recently, three novel collagen VI a-chains, a4, a5, and a6, encoded by the distinct genes Col6a4, GDC-0449 Col6a5, and Col6a6 were identified. These chains are composed of seven Nterminal VWA domains, a collagen triple helical region and a Cterminal non-collagenous domain containing two or three Cterminal VWA domains and one or two unique sequences. In addition, the a4 chain carries a Kunitz domain. Their triple helical regions are most similar to that of the a3 chain, and, in general, the recently identified chains resemble this chain. In contrast to the a3 chain, the a4, a5 and a6 chains have highly restricted distributions often associated with basement membranes. Visual examination of the skin of collagen VI deficient mice revealed no obvious abnormalities and light microscope analysis showed a similar appearance of wild type and Col6a1 null skin. This was surprising as not only the a1 chain is lacking in these mice, but the assembly and secretion of the other collagen VI chains is also AG-013736 severely affected Apparently collagen VI is not necessary to maintain the morphology of mouse skin under physiological conditions.