title: Restoring Bcl-x(L) levels benefits a mouse model of spinal muscular atrophy.
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-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.
authors.affiliation: Department of Neurology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei 100, Taiwan.
authors.forename: Li-Kai
authors.initials: LK
authors.lastname: Tsai
authors.forename: Ming-Shiun
authors.initials: MS
authors.lastname: Tsai
authors.forename: Chen-Hung
authors.initials: CH
authors.lastname: Ting
authors.forename: Sue-Hong
authors.initials: SH
authors.lastname: Wang
authors.forename: Hung
authors.initials: H
authors.lastname: Li
mesh_terms: 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*
chemical_list: D051020:bcl-X Protein