Abstract
The microphthalmic mouse with a mutation at the locus of the microphthalmia-associated transcriptional factor (MITF) gene exhibits masticatory dysfunction due to impaired masseter muscle development and needs to be fed with powdered diet. However, the effects of MITF mutation on masseter muscle remain poorly understood. Here, we show that masseter muscle mass is markedly decreased in MITF-mutant mice (mi/mi), in contrast to the corresponding tibialis anterior and soleus muscles. The area of fibrosis and degree of myocyte apoptosis were strikingly increased in the masseter muscle of mi/mi. The expression of muscle-specific microRNAs (miR-1, miR-206, and miR-133a), which are necessary for proper skeletal muscle development and function, was strongly suppressed in the masseter muscle of mi/mi during development. In addition, the regulation of reactive oxygen species production, calcium homeostasis via sarcoendoplasmic reticulum calcium transport and autophagic activity, which are important for maintaining skeletal muscle mass and function, were all altered in the masseter muscle of mi/mi. These results indicate that MITF is required for masseter muscle growth and development.