THE NEURONAL VOLTAGE-GATED SODIUM-CHANNEL, SCN8A, IS ESSENTIAL FOR POSTNATAL MATURATION OF SPINAL, BUT NOT OCULOMOTOR, MOTOR UNITS

Mice with a nontargeted transgene insertion at the motor endplate dise ase (med) locus (med(tg)) contain a deletion of a novel gene encoding a neuronal voltage-gated sodium channel, designated Scn8a (4). We char acterized severe? skeletal muscle atrophy beginning by Postnatal Day 1 0 (P10) and death by P20 in the med(tg) mouse. Denervation was functio nal, rather than structural, since the Scn8a mutation was not accompan ied by retraction of neuromuscular contacts, motoneuron death, or decr eased motoneuron soma diameter. Although pathology consistent with den ervation was seen in both hindlimb and forelimb musculature, the postn atal maturation of the extraocular muscles was not altered, The onset of paralysis is likely coincident with the time that the Scn8a sodium channel normally assumes a critical role in the initiation and/or prop agation of action potentials in spinal motoneurons. By contrast, the l ack of consequences for extraocular muscle suggests that the Scn8a vol tage-gated sodium channel may be of relatively minor importance for oc ulomotor motoneurons. (C) 1996 Academic Press, Inc.