Journal
MOLECULAR THERAPY
Volume 13, Issue 6, Pages 1149-1155Publisher
CELL PRESS
DOI: 10.1016/j.ymthe.2006.02.008
Keywords
spinal muscular atrophy model mice; Bax-dependent apoptosis; motoneuron degeneration; motoneuron diseases
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Spinal muscular atrophy (SMA) is the most common genetic motoneuron degenerative disorder, but the mechanism(s) of motoneuron degeneration is unclear. We previously generated SMA model mice, which genotypically and phenotypically mimicked human SMA patients, by a combination of knockout and transgenic techniques. Here, we used these SMA model mice to decipher the apoptotic mechanism(s) involved in SMA motoneuron degeneration. We found a significant increase in proapoptotic Bax expression in the spinal cords of SMA mice in comparison with their wild-type littermates. After crossing SMA mice with Box knockout mice, we produced in vivo evidence indicating that Bax protein plays an important role in the degeneration of SMA spinal motoneurons. Progeny Bax-deficient SMA mice showed milder disease severity, longer life spans, and significant increases in spinal motoneuron densities compared to SMA littermates with wildtype Box genes. Our results strongly suggest that suppression of Bax-involved apoptosis has the potential for amelioration of SMA.
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