Muscular Dysgenesis in the Mouse (mdg/mdg)

Abstract

Muscular dysgenesis (mdg/mdg), transmitted as an autosomal recessive trait in the mouse, is characterized by a total inability to contract any skeletal muscle. In addition, there is fixation of posture at multiple joints at the time of birth (arthrogryposis multiplex congenita). This muscular disorder has been studied by light, phase and electron microscopic techniques, combined with cytochemical methods. The homozygous mutant fetuses (mdg/mdg) and their littermates (+/?) were studied at time intervals of from 18 to 20 days of gestation. Four litters of non mdg mice (+/+) resulting from thematings of Harvard white mice also served as controls. Structural alterations were found both in cardiac and skeletal intrafusal and extrafusal muscle. These changes were characterized by a deviation in the course of muscle development. The most significant change was considered to be in the contractile substance, particularly in the Z band structure. Changes in the sarcotubular system and the retarded development of the motor end plate appeared to result from this primary abnormality in contractile substance. Contraction bodies were consistently located close to the motor end plate. The presence of contraction bodies, and the failure of muscle-tendon junctions to form seemed to be related t o an alteration of the contractile filaments. Limited longitudinal growth of the muscle fibers and disorganization of myofibrils were attributed to the incomplete development of the Z band.