Transgenic mouse model for spinal muscular atrophy: morphological characterization and gene therapy approach

Spinal muscular atrophy is an autosomal recessive disease characterized by motor neuron loss leading a progressive paralysis of skeletal muscles. In this study, we characterized at morphological level, spinal cord and brain of transgenic SMAdelta7 mouse model, mimicking SMA type II, in order to better define which neuron populations are more vulnerable to SMA progression during development. We found that larger motor neurons innervating proximal muscles result more vulnerable to loss and that degeneration is not restricted to lower motorneurons, but the upper motor system is also involved in SMA progression. These studies allowed to have a read out to assess the efficacy of gene therapy approaches after restoration of both FL-SMN and a-SMN protein levels by using adeno-viral vectors.