Increased density of satellite cells in the absence of fibre degeneration in muscle of myotonic mice.

A mutant mouse with a hereditary myotonia, 'arrested development of righting response', ADR, was investigated with respect to mononucleated cell populations in skeletal muscle. Upon enzymatic dissociation of different muscles from mice aged between 15 and 120 days, a 3- to 5-fold higher yield of mononucleated cells per muscle fresh weight was obtained from mice with the ADR syndrome than from control mice. Clonal cell culture showed that the absolute number of cells with myogenic potential was increased and that mutant clones had shorter generation times than wild-type controls. Morphological differentiation of ADR myotubes was indistinguishable from that of the controls. Light microscopy confirmed the presence of increased numbers of mononucleated cells per muscle volume. At the ultrastructural level, there were 3.3 times as many satellite cells (the myogenic stem cells of mature muscle) per myofibre nucleus in ADR than in controls. Because no fibre degeneration was observed in the ADR mutant, we conclude that the enlarged mutant satellite cell pool is not a result of compensatory proliferation but is a consequence of fibre-type transformation and/or delayed maturation of the myotonic muscle.