Fig. 1.

Muscle denervation increases skeletal muscle Gadd45a mRNA and causes muscle atrophy through an ATF4-independent pathway. Wild-type mice and muscle-specific ATF4 knockout (ATF4 mKO) mice were subjected to unilateral hindlimb denervation for 1 wk, and then bilateral hindlimb muscles were harvested. Wild-type mice were littermates of ATF4 mKO mice and lacked the MCK-Cre transgene. A: Gadd45a mRNA levels in the tibialis anterior (TA) muscles were quantified by quantitative real-time RT-PCR (qPCR). Gadd45a mRNA levels in denervated muscles were normalized to levels in contralateral innervated muscles. B: wet weights of TA and gastrocnemius muscles. A and B: data are means ± SE from 6–10 mice/genotype. NS denotes P ≥ 0.05. C: quantification of TA muscle fiber size. Left, mean fiber diameter ± SE. Right, fiber size distributions. n = 4 muscles/condition. D: representative hematoxylin and eosin images from C.