Restoring Bcl-xL levels benefits a mouse model of spinal muscular atrophy
Journal
Neurobiology of Disease
Journal Volume
31
Journal Issue
3
Pages
361-367
Date Issued
2008
Author(s)
Abstract
Currently, no curative treatment is available for spinal muscular atrophy (SMA). Since the degeneration of spinal motor neurons in SMA is mediated by apoptosis, over-expression of an anti-apoptotic factor, Bcl-xL, may benefit SMA. Here, we crossed a mouse model of SMA with Bcl-xL transgenic mice to create SMA/Bcl-xL mice. The Bcl-xL expression in the spinal neurons of SMA/Bcl-xL mice was nearly double that in SMA mice. SMA/Bcl-xL mice showed preserved motor function, normalized electrophysiological tests, diminished muscle atrophy, and less motor neuron degeneration. In addition, the life span of SMA/Bcl-xL mice was 1.5 times longer than that of SMA mice. Therefore, over-expression of Bcl-xL has a potential for amelioration of SMA, and Bcl-xL may be another attractive therapeutic target other than survival motor neuron (SMN) protein for use in future drug screening for SMA. ? 2008 Elsevier Inc. All rights reserved.
SDGs
Other Subjects
protein bcl xl; animal cell; animal experiment; animal model; animal tissue; article; cell structure; controlled study; electrophysiology; lifespan; motor performance; mouse; nonhuman; priority journal; protein expression; spinal cord nerve cell; spinal muscular atrophy; transgenic mouse; Animals; Apoptosis; bcl-X Protein; Cell Survival; Crosses, Genetic; Disease Models, Animal; Drug Design; Drug Evaluation, Preclinical; Gene Therapy; Humans; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Motor Neurons; Muscular Atrophy; Muscular Atrophy, Spinal; Nerve Degeneration; Spinal Cord; Survival Rate
Type
journal article