TY - JOUR AB - Charcot‑Marie‑Tooth disease (CMT) is the most common inherited neurological disorder of the peripheral nervous system. The major subtype, CMT type 1A (CMT1A), accounts for ~40% of CMT cases and is characterized by distal muscle atrophy and gait disturbances. Short hairpin (sh) RNA sequences are potentially advantageous therapeutic tools for distal muscle atrophy‑induced gait disturbance. Therefore, the current study focused on the effects of an optimal shRNA injection using the myostatin (mstn) gene inhibition system. shLenti‑Mstn A demonstrated significant suppression of endogenous mstn gene expression (>40%) via RT‑qPCR following direct injection into the gastrocnemius and rectus femoris of the hind limb in C22 mice. The results also reported that shLenti‑Mstn A treatment increased muscle mass and size of the hind limbs compared with mock‑treated mice via measurement of the mass of injected muscles and magnetic resonance imaging study. Furthermore, electrophysiological measurement using a Nicolet Viking Quest device revealed significantly improved compound muscle action potential (CMAP) in shLenti‑Mstn A‑treated mice compared with the mock group (P<0.05) whereas nerve conduction velocity (NCV) showed no difference between groups. The shLenti‑Mstn A treatment directly affected increased muscle regeneration, including mass and size, but not regeneration of peripheral nerve. Additionally, shLenti‑Mstn A treatment significantly enhanced mobility, including locomotor coordination (P<0.01) and grip strength of the hindlimbs (P<0.01). Furthermore, MotoRater analysis using real‑time recording with a high‑speed camera revealed that shLenti‑Mstn‑treated mice exhibited an improved walking pattern in terms of step length, base support and duty factor compared with the mock group. It was hypothesized that treatment with shLenti‑Mstn A may provide a novel therapeutic strategy for improving gait in patients with CMT1A. AD - Department of Health Sciences and Technology, Samsung Advanced Institute for Health Science and Technology (SAIHST), Sungkyunkwan University, Seoul 06351, Republic of Korea Department of Biochemistry, College of Medicine, Dong‑A University, Busan, South Gyeongsang 49201, Republic of Korea Department of Biological Sciences, Laboratory of Stem Cell Research and Biotechnology, Hyupsung University, Hwasung‑si, Gyeonggi 18330, Republic of Korea Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea Stem Cell and Regenerative Medicine Institute, Samsung Medical Center, Seoul 06351, Republic of Korea Department of Neurology, Kyung Hee University Hospital at Gangdong, Kyung Hee University School of Medicine, Seoul 05278, Republic of Korea Department of Biological Sciences, Kongju National University, Gongju, Chungcheong 32588, Republic of Korea AU - Doo,Hyun ,Myung AU - Hong,Young,Bin AU - Han,Jiyou AU - Moon,Hyo,Won AU - Hwang,Hyun AU - Kwak,Geon AU - Nam,Soo ,Hyun AU - Kim,Sang ,Beom AU - Chung,Ki ,Wha AU - Kim,Jong ,Hyun AU - Choi,Byung‑Ok DA - 2020/12/01 DO - 10.3892/mmr.2020.11579 EP - 4955 IS - 6 JO - Mol Med Rep KW - Charcot‑Marie‑Tooth disease gait muscle regeneration short hairpin RNA myostatin PY - 2020 SN - 1791-2997 1791-3004 SP - 4947 ST - Short hairpin RNA treatment improves gait in a mouse model of Charcot‑Marie‑Tooth disease type 1A T2 - Molecular Medicine Reports TI - Short hairpin RNA treatment improves gait in a mouse model of Charcot‑Marie‑Tooth disease type 1A UR - https://doi.org/10.3892/mmr.2020.11579 VL - 22 ER -