Restoring Bcl-x(L) levels benefits a mouse model of spinal muscular atrophy.
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-x(L), may benefit SMA. Here, we crossed a mouse model of SMA with Bcl-x(L) transgenic mice to create SMA/Bcl-x(L) mice. The Bcl-x(L) expression in the spinal neurons of SMA/Bcl-x(L) mice was nearly double that in SMA mice. SMA/Bcl-x(L) mice showed preserved motor function, normalized electrophysiological tests, diminished muscle atrophy, and less motor neuron degeneration. In addition, the life span of SMA/Bcl-x(L) mice was 1.5 times longer than that of SMA mice. Therefore, over-expression of Bcl-x(L) has a potential for amelioration of SMA, and Bcl-x(L) may be another attractive therapeutic target other than survival motor neuron (SMN) protein for use in future drug screening for SMA.
Tsai
Li-Kai
LK
Department of Neurology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei 100, Taiwan.
Tsai
Ming-Shiun
MS
Ting
Chen-Hung
CH
Wang
Sue-Hong
SH
Li
Hung
H
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D003433:Crosses, Genetic; D004195:Disease Models, Animal; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000378:metabolism* / Q000473:pathology; D009133:Muscular Atrophy / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D009134:Muscular Atrophy, Spinal / Q000235:genetics / Q000378:metabolism* / Q000628:therapy*; D009410:Nerve Degeneration / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D013116:Spinal Cord / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D015996:Survival Rate; D051020:bcl-X Protein / Q000235:genetics / Q000378:metabolism*
D051020:bcl-X Protein