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

Deletion of the murine survival of motor neuron gene (SMN) exon 7 ,t he 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 (SMN∆C15) is dramatically reduced in the motor neuron nuclei and causes a lack of gems associated with large aggregates of coilin, a coiled-bodyspecific protein. These results identify the lack of the nuclear targeting of SMN as the biochemical defect in SMA.