title: Refined characterization of the expression and stability of the SMN gene products.
abstract: Spinal muscular atrophy (SMA) is characterized by degeneration of lower motor neurons and caused by mutations of the SMN1 gene. SMN1 is duplicated in a homologous gene called SMN2, which remains present in patients. SMN has an essential role in RNA metabolism, but its role in SMA pathogenesis remains unknown. Previous studies suggested that in neurons the protein lacking the C terminus (SMN(Delta7)), the major product of the SMN2 gene, had a dominant-negative effect. We generated antibodies specific to SMN(FL) or SMN(Delta7). In transfected cells, the stability of the SMN(Delta7) protein was regulated in a cell-dependent manner. Importantly, whatever the human tissues examined, SMN(Delta7) protein was undetectable because of the instability of the protein, thus excluding a dominant effect of SMN(Delta7) in SMA. A similar decreased level of SMN(FL) was observed in brain and spinal cord samples from human SMA, suggesting that SMN(FL) may have specific targets in motor neurons. Moreover, these data indicate that the vulnerability of motor neurons cannot simply be ascribed to the differential expression or a more dramatic reduction of SMN(FL) in spinal cord when compared with brain tissue. Improving the stability of SMN(Delta7) protein might be envisaged as a new therapeutic strategy in SMA.
authors: Molecular Neurogenetics Laboratory, INSERM U798, Evry and Paris 11 Universities, Evry, France.
authors: Jérémie
authors: J
authors: Vitte
authors: Coralie
authors: C
authors: Fassier
authors: Francesco D
authors: FD
authors: Tiziano
authors: Cécile
authors: C
authors: Dalard
authors: Sabrina
authors: S
authors: Soave
authors: Natacha
authors: N
authors: Roblot
authors: Christine
authors: C
authors: Brahe
authors: Pascale
authors: P
authors: Saugier-Veber
authors: Jean Paul
authors: JP
authors: Bonnefont
authors: Judith
authors: J
authors: Melki
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology; D002460:Cell Line; D002478:Cells, Cultured; D017362:Cyclic AMP Response Element-Binding Protein / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009134:Muscular Atrophy, Spinal / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000737:chemistry / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D055532:SMN Complex Proteins; D017384:Sequence Deletion; D055533:Survival of Motor Neuron 1 Protein; D055540:Survival of Motor Neuron 2 Protein
chemical_list: D000906:Antibodies; D017362:Cyclic AMP Response Element-Binding Protein; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; D055532:SMN Complex Proteins; C526471:SMN1 protein, human; C526477:SMN2 protein, human; C526472:Smn1 protein, mouse; D055533:Survival of Motor Neuron 1 Protein; D055540:Survival of Motor Neuron 2 Protein
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