title: Identification of the mouse neuromuscular degeneration gene and mapping of a second site suppressor allele.
abstract: The nmd mouse mutation causes progressive degeneration of spinal motor neurons and muscle atrophy. We identified the mutated gene as the putative transcriptional activator and ATPase/DNA helicase previously described as Smbp2, Rip1, Gf1, or Catf1. Mutations were found in two alleles-a single amino acid deletion in nmdJ and a splice donor mutation in nmd2J. The selective vulnerability of motor neurons is striking in view of the widespread expression of this gene, although the pattern of degeneration may reflect a specific threshold since neither allele is null. In addition, the severity of the nmd phenotype is attenuated in a semidominant fashion by a major genetic locus on chromosome (Chr) 13. The identification of the nmd gene and mapping of a major suppressor provide new opportunities for understanding mechanisms of motor neuron degeneration.
authors.affiliation: The Jackson Laboratory, Bar Harbor, Maine 04609, USA. gac@jax.org
authors.forename: G A
authors.initials: GA
authors.lastname: Cox
authors.forename: C L
authors.initials: CL
authors.lastname: Mahaffey
authors.forename: W N
authors.initials: WN
authors.lastname: Frankel
mesh_terms: D000251:Adenosine Triphosphatases / Q000737:chemistry / Q000235:genetics*; D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping; D006224:Cricetinae; D004265:DNA Helicases / Q000737:chemistry / Q000235:genetics*; D005091:Exons; D016153:Genes, Suppressor; D006801:Humans; D051379:Mice; D008808:Mice, Inbred CBA; D008818:Mice, Neurologic Mutants; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000473:pathology; D009410:Nerve Degeneration / Q000235:genetics* / Q000473:pathology; D009468:Neuromuscular Diseases / Q000235:genetics* / Q000473:pathology; D015183:Restriction Mapping; D017384:Sequence Deletion; D013116:Spinal Cord / Q000473:pathology
chemical_list: D000251:Adenosine Triphosphatases; D004265:DNA Helicases