Toshifumi Yokota1, Yuko Miyagoe-Suzuki, Takaaki Ikemoto, Ryoichi Matsuda, Shin'ichi Takeda. 1. Department of Medical Genetics, School of Human Development, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada; Department of Molecular Therapy, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1, Ogawa-higashi, Kodaira, Tokyo, 187-8502, Japan.
Abstract
INTRODUCTION: α1-syntrophin, a member of the dystrophin complex, recruits membrane molecules, including aquaporin-4, at the sarcolemma. The physiological functions of α1-syntrophin are poorly understood. METHODS: We examined the physiological characteristics of α1-syntrophin-deficient muscles under osmotic stress conditions to test the possibility that mutant muscles are less tolerant of osmotic shock. RESULTS: Isolated muscle bundles from mutant mice showed markedly reduced force production after hypo-osmotic shock. In addition, the mutant muscle bundles showed delayed recovery of specific gravity after being exposed to hypo-osmotic conditions. Two consecutive exercise tests on the treadmill revealed their performance in the second test was significantly lower than for wild-type mice. Furthermore, mutant mice had higher serum lactate concentrations after treadmill exercise. CONCLUSIONS: Although the lack of α1-syntrophin from the sarcolemma does not lead to muscle degeneration, our results suggest that it may be partly involved in the pathophysiology of dystrophin-deficient Duchenne muscular dystrophy.
INTRODUCTION: α1-syntrophin, a member of the dystrophin complex, recruits membrane molecules, including aquaporin-4, at the sarcolemma. The physiological functions of α1-syntrophin are poorly understood. METHODS: We examined the physiological characteristics of α1-syntrophin-deficient muscles under osmotic stress conditions to test the possibility that mutant muscles are less tolerant of osmotic shock. RESULTS: Isolated muscle bundles from mutant mice showed markedly reduced force production after hypo-osmotic shock. In addition, the mutant muscle bundles showed delayed recovery of specific gravity after being exposed to hypo-osmotic conditions. Two consecutive exercise tests on the treadmill revealed their performance in the second test was significantly lower than for wild-type mice. Furthermore, mutant mice had higher serum lactate concentrations after treadmill exercise. CONCLUSIONS: Although the lack of α1-syntrophin from the sarcolemma does not lead to muscle degeneration, our results suggest that it may be partly involved in the pathophysiology of dystrophin-deficient Duchenne muscular dystrophy.
Authors: Min Jeong Kim; Nicholas P Whitehead; Kenneth L Bible; Marvin E Adams; Stanley C Froehner Journal: Hum Mol Genet Date: 2019-02-01 Impact factor: 6.150