Nuclear targeting defect of SMN lacking the C-terminus in a mouse model of spinal muscular atrophy

Hum Mol Genet. 2000 Mar 22;9(5):849-58. doi: 10.1093/hmg/9.5.849.


Deletion of the murine survival of motor neuron gene (SMN) exon 7, the most frequent mutation found in spinal muscular atrophy (SMA) patients, directed to neurons but not to skeletal muscle, enabled generation of a mouse model of SMA providing evidence that motor neurons are the primary target of the gene defect. Moreover, the mutated SMN protein (SMNDeltaC15) is dramatically reduced in the motor neuron nuclei and causes a lack of gems associated with large aggregates of coilin, a coiled-body-specific protein. These results identify the lack of the nuclear targeting of SMN as the biochemical defect in SMA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Cell Nucleus / metabolism*
  • Cyclic AMP Response Element-Binding Protein
  • DNA Primers
  • Disease Models, Animal
  • Exons
  • Gene Deletion
  • Genes, Lethal
  • Homozygote
  • Mice
  • Motor Neurons / metabolism
  • Muscular Atrophy, Spinal / genetics*
  • Muscular Atrophy, Spinal / metabolism
  • Nerve Tissue Proteins / chemistry
  • Nerve Tissue Proteins / genetics*
  • Phenotype
  • RNA-Binding Proteins
  • SMN Complex Proteins


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