Lack of type XV collagen causes a skeletal myopathy and cardiovascular defects in mice.

Type XV collagen occurs widely in the basement membrane zones of tissues, but its function is unknown. To understand the biological role of this protein, a null mutation in the Col15a1 gene was introduced into the germ line of mice. Despite the complete lack of type XV collagen, the mutant mice developed and reproduced normally, and they were indistinguishable from their wild-type littermates. However, Col15a1-deficient mice showed progressive histological changes characteristic for muscular diseases after 3 months of age, and they were more vulnerable than controls to exercise-induced muscle injury. Despite the antiangiogenic role of type XV collagen-derived endostatin, the development of the vasculature appeared normal in the null mice. Nevertheless, ultrastructural analyses revealed collapsed capillaries and endothelial cell degeneration in the heart and skeletal muscle. Furthermore, perfused hearts showed a diminished inotropic response, and exercise resulted in cardiac injury, changes that mimic early or mild heart disease. Thus, type XV collagen appears to function as a structural component needed to stabilize skeletal muscle cells and microvessels.

Developmentally regulated expression of cytochrome-c oxidase isoforms in regenerating rat skeletal muscle.

The developmental expression of tissue-specific isoforms of cytochrome-c oxidase (COX) subunit VIII [heart (COX VIII-H) and liver (COX VIII-L)] and the influence of innervation were examined in regenerating fast [extensor digitorum longus (EDL)] and slow (soleus) muscles. In adult muscles, COX VIII-H was the predominant isoform. The COX VIII-L mRNA was expressed 3 days after induction of regeneration, and it progressively decreased after 7, 10, 14, and 30 days of regeneration in both muscles. In contrast, the expression of COX VIII-H mRNA accumulated as myogenesis proceeded to the myotube stage between 7 and 10 days of regeneration and progressively increased to near control levels by 30 days. The influence of innervation on the expression of COX VIII and alpha-actin isoforms was examined in control, innervated, and denervated regenerating muscles at 3 and 10 days. The relative expression of COX VIII-L mRNA in denervated regenerating EDL muscles was significantly greater, while that of COX VIII-H was significantly less than in innervated regenerating EDL muscles after 10 days of regeneration. Similarly, cardiac alpha-actin mRNA levels were elevated in denervated regenerating EDL muscles after 10 days of regeneration. In conclusion, motor innervation influences the transition from the COX VIII-L to COX VIII-H isoform during myogenesis in regenerating muscles.