LRRK2G2019S Gene Mutation Causes Skeletal Muscle Impairment in Animal Model of Parkinson's Disease

ABSTRACT Background While the gradually aggravated motor and non‐motor disorders of Parkinson's disease (PD) lead to progressive disability and frequent falling, skeletal muscle impairment may contribute to this condition. The leucine‐rich repeat kinase2 (LRRK2) is a common disease‐causing gene in PD. Little is known about its role in skeletal muscle impairment and its underlying mechanisms. Methods To investigate whether the mutation in LRRK2 causes skeletal muscle impairment, we used 3‐month‐old (3mo) and 14‐month‐old (14mo) LRRK2G2019S transgenic (TG) mice as a model of PD, compared with the age‐matched littermate wild‐type (WT) controls. We measured the muscle mass and strength, ultrastructure, inflammatory infiltration, mitochondrial morphology and dynamics dysfunction through behavioural analysis, electromyography (EMG), immunostaining, transmission electron microscopy (TEM) and other molecular biology techniques. Results The 3mo‐TG mice display mild skeletal muscle impairment with spontaneous potentials in EMG (increased by 130%, p