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

Tony Frugier , Francesco D. Tiziano , Carmen Cifuentes-Diaz , Pierre Miniou , Natacha Roblot , Andrée Dierich (1, 1) , Marianne Le Meur , Judith Melki

1 IGBMC - Institut de Génétique et de Biologie Moléculaire et Cellulaire

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.

Domaines: Biologie animale

Tony Frugier, Francesco D. Tiziano, Carmen Cifuentes-Diaz, Pierre Miniou, Natacha Roblot, et al.. Nuclear targeting defect of SMN lacking the C-terminus in a mouse model of spinal muscular atrophy. Human Molecular Genetics, 2000, 9 (5), pp.849-858. ⟨10.1093/hmg/9.5.849⟩. ⟨hal-04112669⟩