Neuromyotonia in mice with hereditary myelinopathies

The purpose of this study was to further characterize neuromyotonia in mice with deletions and point mutations of myelin protein genes. Clinical obser vation showed irregular stretching of the hindlimbs, tremor and generalized myokymia in mice with targeted deletions of the genes encoding myelin prot ein zero (P0-/-) or peripheral myelin protein 22 (Pmp22-/-), and Trembler m ice, which carry a point mutation of Pmp22. By electromyography (EMG), we f ound irregular high-frequency bursts of spontaneous motor unit activity and rhythmic doublet or multiplet discharges of motor units in these mouse mod els of human hereditary neuropathies. The EMG signs are typical for neuromy otonia and myokymia, respectively. The activity persisted after a proximal nerve section in many cases, localizing the generator to the peripheral ner ve or the muscle. We now show that blocking neuromuscular transmission with suxamethonium abolished the spontaneous activity, ruling out a muscle orig in. Phenytoin ameliorated the motor behavior. Taken together, our study sho ws that neuromyotonia develops in different mouse models of hereditary myel inopathies. This indicates that spontaneous motor unit activity may underli e neuromyotonia, which is occasionally observed in Charcot-Marie-Tooth dise ase. These animal models will be useful to study the pathogenesis of neurom yotonia. (C) 2000 John Wiley & Sons, Inc.