Abnormal motor phenotype in the SMNΔ7 mouse model of spinal muscular atrophy

Spinal muscular atrophy (SMA) is a recessive motor neuron disease that affects motor neurons in the anterior horn of the spinal cord. SMA results from the reduction of SMN (survival motor neuron) protein. Even though SHIN is ubiquitously expressed, motor neurons are more sensitive to the reduction in SMN than other cell types. We have previously generated mouse models of SMA with varying degrees of clinical severity. So as to more clearly understand the pathogenesis of motor neuron degeneration in SMA, we have characterized the phenotype of the SMN Delta 7 SMA mouse which normally lives for 13.6 +/- 0.7 days. These mice are smaller than their non-SMA littermates and begin to lose body mass at 10.4 +/- 0.4 days. SMN Delta 7 SMA mice exhibit impaired responses to surface righting, negative geotaxis and cliff aversion but not to tactile stimulation. Spontaneous motor activity and grip strength are also significantly impaired in SMN Delta 7 SMA mice. In summary, we have demonstrated an impairment of neonatal motor responses in SMN Delta 7 SMA mice. This phenotype characterization could be used to assess the effectiveness of potential therapies for SMA. (c) 2007 Elsevier Inc. All rights reserved.