Fiber-Type Composition and Structural Analysis of the Tibialis Anterior Muscle in Collagen VI Knockout Mice

Collagen VI is a major protein that is secreted into the ECM, of skeletal muscle, tendons, skin, bones, adipose tissue and the nervous system. It plays a mechanic role of anchoring cells to the surrounding matrix, and a cytoprotective role through intracellular signaling pathways. Collagen VI-related myopathies (COL6-RM) are a group of muscle disorders caused by mutations in one of the collagen VI genes (COL6A1, COL6A2, COL6A3). In patients, they are characterized by hypermobility of distal joints alongside contractures of proximal joints and muscle hypotonia, which can progress to respiratory failure. Although the overall clinical phenotype is considerably milder in mice, the disease is well recapitulated at the histological and molecular levels. This study examined the Tibialis Anterior muscle of wild-type and knockout mice at two different ages (6 and 24 months), analyzing key histological and morphometric features of muscle pathology, including fiber cross-sectional area, and minimal Feret’s diameter, as well as muscle fiber-type composition. Our findings show that the muscle of young Col6a1-/- mice closely resembles that of older wild-type animals, suggesting that the absence of collagen VI leads to premature muscle ageing.