Caveolin-3 is a muscle-specific membrane protein that serves as a scaffold of various molecules. As previously reported, caveolin-3 deficiency causes muscle degeneration in mice. In the present study, gene expression profiles, analyzed in the skeletal muscles of caveolin-3 deficient mice using the DNA microarray technique, showed that the gene of osteopontin, a versatile regulator of inflammation and tissue repair, was significantly down-regulated. This is in contrast to mdx mice showing a markedly up-regulated osteopontin gene in their skeletal muscles. Recently, osteopontin has been reported to be important in the pathogenesis of muscular dystrophy. We examined whether up-regulated osteopontin gene expression in mdx muscles is altered by the deficiency of caveolin-3. To this end, we developed caveolin-3 and dystrophin double-deficient mice and used them for the analysis. Levels of osteopontin mRNA and protein in the double-deficient mice clearly decreased compared with those in mdx mice.