Survival motor neuron SMN1 and SMN2 gene promoters: Identical sequences and differential expression in neurons and non-neuronal cells

Bernadett Boda, Christophe Mas, Catherine Giudicelli, Virginie Nepote, Fabien Guimiot, Béatrice Levacher, Agnes Zvara, Miklos Santha, Isabelle LeGall, Michel Simonneau

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Spinal muscular atrophy (SMA) is a recessive disorder involving the loss of motor neurons from the spinal cord. Homozygous absence of the survival of motor neuron 1 gene (SMN1) is the main cause of SMA, but disease severity depends primarily on the number of SMN2 gene copies. SMN protein levels are high in normal spinal cord and much lower in the spinal cord of SMA patients, suggesting neuron-specific regulation for this ubiquitously expressed gene. We isolated genomic DNA from individuals with SMN1 or SMN2 deletions and sequenced 4.6 kb of the 5′ upstream regions of the these. We found that these upstream regions, one of which is telomeric and the other centromeric, were identical. We investigated the early regulation of SMN expression by transiently transfecting mouse embryonic spinal cord and fibroblast primary cultures with three transgenes containing 1.8, 3.2 and 4.6, respectively, of the SMN promoter driving β-galactosidase gene expression. The 4.6 kb construct gave reporter gene expression levels five times higher in neurons than in fibroblasts, due to the combined effects of a general enhancer and a non-neuronal cell silencer. The differential expression observed in neurons and fibroblasts suggests that the SMN genes play a neuron-specific role during development. An understanding of the mechanisms regulating SMN promoter activity may provide new avenues for the treatment of SMA.

Original languageEnglish
Pages (from-to)729-737
Number of pages9
JournalEuropean Journal of Human Genetics
Volume12
Issue number9
DOIs
Publication statusPublished - Sep 1 2004

Keywords

  • Neuron
  • Promoter
  • SMN

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Fingerprint Dive into the research topics of 'Survival motor neuron SMN1 and SMN2 gene promoters: Identical sequences and differential expression in neurons and non-neuronal cells'. Together they form a unique fingerprint.

  • Cite this