Powell J A
Department of Biological Sciences, Smith College, Northampton, Massachusetts 01063.
FASEB J. 1990 Jul;4(10):2798-808. doi: 10.1096/fasebj.4.10.2197156.
Muscular dysgenesis, caused by an autosomal recessive lethal mutation (mdg) in mice, is characterized by an absence of contraction of skeletal muscle. A historical review of the investigation of this disorder is presented. The early studies of the morphological and physiological aspects of the disorder in vivo and in vitro presented evidence for dysfunction in the skeletal muscle excitation-contraction (E-C) system, and thus suggested that skeletal muscle was the primary target of dysfunction in dysgenesis. Subsequent evidence, including the phenomenon of rescue (restoration of contraction) of dysgenic muscle in culture by spinal cord cells, argued for involvement of the nervous system in the disorder. Experiments demonstrating that dysgenic muscle lacks the slow calcium current associated with E-C coupling, and the protein (the dihydropyridine receptor) also associated with such coupling, led to the discovery of the probable site of the mutation: the gene for the alpha 1 subunit of the dihydropyridine receptor. The neuronal involvement hypothesis was further countered by several lines of evidence, including the phenomenon of fusion of nonmyogenic normal cells with dysgenic myotubes in cocultures of normal cells and dysgenic muscle. The use of the mutant as a model for studying the development of normal skeletal muscle is discussed and future avenues of research are explored.
肌肉发育不全是由小鼠常染色体隐性致死突变（mdg）引起的，其特征是骨骼肌缺乏收缩能力。本文对该疾病的研究进行了历史回顾。早期对该疾病体内和体外形态学及生理学方面的研究表明，骨骼肌兴奋-收缩（E-C）系统存在功能障碍，因此提示骨骼肌是发育不全中功能障碍的主要靶点。随后的证据，包括脊髓细胞在培养中对发育不全肌肉的挽救（收缩恢复）现象，表明神经系统参与了该疾病。实验表明，发育不全的肌肉缺乏与E-C偶联相关的慢钙电流以及同样与这种偶联相关的蛋白质（二氢吡啶受体），从而发现了可能的突变位点：二氢吡啶受体α1亚基的基因。神经元参与假说还受到了几条证据的反驳，包括在正常细胞与发育不全肌肉的共培养中，非肌源性正常细胞与发育不全肌管融合的现象。本文讨论了利用该突变体作为研究正常骨骼肌发育模型的情况，并探索了未来的研究途径。
