Reduced survival motor neuron (Smn) gene dose in mice leads to motor neuron degeneration: An animal model for spinal muscular atrophy type III

Sibylle Jablonka, Bertold Schrank, Martina Kralewski, Wilfried Rossoll, Michael Sendtner

Research output: Contribution to journalArticlepeer-review

144 Scopus citations

Abstract

Spinal muscular atrophy (SMA) is caused by deletion or specific mutations of the telomeric survival motor neuron (SMN) gene on human chromosome 5. The human SMN gene, in contrast to the Smn gene in mouse, is duplicated and the centromeric copy on chromosome 5 codes for transcripts which preferentially lead to C-terminally truncated SMN protein. Here we show that a 46% reduction of Smn protein levels in the spinal cord of Smn heterozygous mice leads to a marked loss of the cytoplasmic Smn pool and motor neuron degeneration resembling spinal muscular atrophy type 3. Smn heterozygous mice described here thus represent a model for the human disease. These mice could allow screening for SMA therapies and help in gaining further understanding of the pathophysiological events leading to motor neuron degeneration in SMA.

Original languageEnglish (US)
Pages (from-to)341-346
Number of pages6
JournalHuman molecular genetics
Volume9
Issue number3
DOIs
StatePublished - Feb 12 2000

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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