Identification and characterization of a mouse homologue of the spinal muscular atrophy-determining gene, survival motor neuron

Gene. 1997 Dec 19;204(1-2):47-53. doi: 10.1016/s0378-1119(97)00510-6.

Abstract

Spinal muscular atrophy (SMA), the second most common fatal, autosomal recessive disease of infants, manifests as generalized muscle weakness. The most severe form (Type I, Werdnig-Hoffmann disease) is associated with quadriplegia, respiratory muscle paralysis and death in infancy. Less severe forms are classified as Type II and Type III, based on age of onset and ultimate motor disability. Some spinal motor neurons show chromatolysis and the number of these cells is decreased. Recently, SMA has been mapped to chromosome 5q11.2-13.3 (Gilliam et al., 1990), a region that contains three candidate genes: Survival Motor Neuron (SMN) (Lefebvre et al., 1995); Neuronal Apoptosis Inhibitory Protein (NAIP) (Roy et al., 1995); and p44, a subunit of transcription factor II H (TFIIH) (Carter et al., 1995; Bürglen et al., 1997). Homozygous deletions or deleterious mutations in SMN are present in all SMA patients, and in some affected individuals, deletions have been identified in one or both of the other genes. These extensive deletions may be associated with a more severe phenotype. We have identified and characterized the mouse homologue of SMN, MoSMN, which is 82% identical to SMN at the amino-acid level. Unlike the duplicated human SMN, MoSMN is present in single copy. Like its human counterpart, MoSMN is ubiquitously expressed, but unlike SMN, MoSMN does not appear to be alternatively spliced. In-situ hybridization analysis of the mouse nervous system revealed that MoSMN mRNA is expressed in spinal cord and throughout the brain, with relatively higher levels of expression in the hippocampus and cerebellum.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alternative Splicing
  • Amino Acid Sequence
  • Animals
  • Cyclic AMP Response Element-Binding Protein
  • Gene Dosage
  • Gene Expression
  • Humans
  • Mice
  • Molecular Sequence Data
  • Muscular Atrophy, Spinal / genetics*
  • Nerve Tissue Proteins / genetics*
  • RNA Precursors
  • RNA-Binding Proteins
  • SMN Complex Proteins
  • Sequence Homology, Amino Acid
  • Tissue Distribution

Substances

  • Cyclic AMP Response Element-Binding Protein
  • Nerve Tissue Proteins
  • RNA Precursors
  • RNA-Binding Proteins
  • SMN Complex Proteins