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

Spinal muscular atrophy (SMA) is caused by deletion or specific mutations o f 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 th e centromeric copy on chromosome 5 codes for transcripts which preferential ly lead to C-terminally truncated SMN protein. Here we show that a 46% redu ction of Smn protein levels in the spinal cord of Smn heterozygous mice lea ds to a marked loss of the cytoplasmic Smn pool and motor neuron degenerati on resembling spinal muscular atrophy type 3. Smn heterozygous mice describ ed here thus represent a model for the human disease. These mice could allo w screening for SMA therapies and help in gaining further understanding of the pathophysiological events leading to motor neuron degeneration in SMA.