Identification of the mouse neuromuscular degeneration gene and mapping ofa second site suppressor allele

The nmd mouse mutation causes progressive degeneration of spinal motor neur ons and muscle atrophy. We identified the mutated gene as the putative tran scriptional activator and ATPase/DNA helicase previously described as Smbp2 , Rip1, Gf1, or Catf1. Mutations were found in two alleles-a single amino a cid deletion in nmd(J) and a splice donor mutation in nmd(2J). The selectiv e vulnerability of motor neurons is striking in view of the widespread expr ession of this gene, although the pattern of degeneration may reflect a spe cific threshold since neither allele is null. In addition, the severity of the nmd phenotype is attenuated in a semidominant fashion by a major geneti c locus on chromosome (Chr) 13. The identification of the nmd gene and mapp ing of a major suppressor provide new opportunities for understanding mecha nisms of motor neuron degeneration.