Identification of the Mouse Neuromuscular Degeneration Gene and Mapping of a Second Site Suppressor Allele

• Published in: Neuron (Cambridge, Mass.) Vol. 21; no. 6; pp. 1327 - 1337
• Main Authors: Cox, Gregory A, Mahaffey, Connie L, Frankel, Wayne N
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.12.1998
• Subjects: Adenosine Triphosphatases - chemistry; Adenosine Triphosphatases - genetics; Alleles; Amino Acid Sequence; Animals; Base Sequence; Catf1 gene; chromosome 13; Chromosome Mapping; Cricetinae; DNA Helicases - chemistry; DNA Helicases - genetics; Exons; Genes, Suppressor; Gf1 gene; Humans; Mice; Mice, Inbred CBA; Mice, Neurologic Mutants; Molecular Sequence Data; Muscle, Skeletal - pathology; Nerve Degeneration - genetics; Nerve Degeneration - pathology; Neuromuscular Diseases - genetics; Neuromuscular Diseases - pathology; nmd gene; Restriction Mapping; Rip1 gene; Sequence Deletion; Smbp2 gene; Spinal Cord - pathology
• ISSN: 0896-6273; 1097-4199
• DOI: 10.1016/S0896-6273(00)80652-2

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 nmd J and a splice donor mutation in nmd 2J. 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.