Loss of LAP2α Delays Satellite Cell Differentiation and Affects Postnatal Fiber-Type Determination

Lamina-associated polypeptide 2α (LAP2α) is a nucleoplasmic protein implicated in cell cycle regulation through its interaction with A-type lamins and the retinoblastoma protein. Mutations in lamin A/C and LAP2α cause late onset striated muscle diseases, but the molecular mechanisms are poorly understood. To study the role of LAP2α in skeletal muscle function and postnatal tissue homeostasis, we generated complete and muscle-specific LAP2α knockout mice. Whereas overall muscle morphology, function, and regeneration were not detectably affected, the myofiber-associated muscle stem cell pool was increased in complete LAP2α knockout animals. At molecular level, the absence of LAP2α preserved the stem cell-like phenotype of Lap2α−/− primary myoblasts and delayed their in vitro differentiation. In addition, loss of LAP2α shifted the myofiber-type ratios of adult slow muscles toward fast fiber types. Conditional Cre-mediated late muscle-specific ablation of LAP2α affected early stages of in vitro myoblast differentiation, and also fiber-type determination, but did not change myofiber-associated stem cell numbers in vivo. Our data demonstrate multiple and distinct functions of LAP2α in muscle stem cell maintenance, early phases of myogenic differentiation, and muscle remodeling.