title: Bcl-2 sensitivity differentiates two pathways for motoneuronal death in the wobbler mutant mouse.
abstract: The molecular events leading to motoneuronal death are still poorly understood. In mammals, the bcl-2 proto-oncogene, which encodes a membrane-associated protein, has been shown to suppress both developmental motoneuronal death and experimental axotomy-induced motoneuronal death. We assessed a potential protective effect of Bcl-2 on pathological motoneuronal death processes in adult rodents. We took advantage of the murine mutant wobbler, which undergoes progressive degeneration of the spinal and brainstem motoneurons. A hybrid carrying both the wobbler mutation and the human bcl-2 transgene under the control of the neuron-specific enolase promoter was produced. Although Bcl-2 protected spinal and brainstem motoneurons from developmental death and the postnatal motoneurons of the facial nucleus from axotomy-induced death, the pathological motoneuronal death was not altered in the adult hybrid. These results demonstrate that Bcl-2 sensitivity distinguishes at least two different motoneuronal death pathways in the wobbler mutant. They support the hypothesis that experimental and pathological motoneuronal death are dependent on different cellular mechanisms.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U421, Créteil, France.
authors.forename: M
authors.initials: M
authors.lastname: Coulpier
authors.forename: M P
authors.initials: MP
authors.lastname: Junier
authors.forename: M
authors.initials: M
authors.lastname: Peschanski
authors.forename: P A
authors.initials: PA
authors.lastname: Dreyfus
mesh_terms: D000818:Animals; D016923:Cell Death; D015870:Gene Expression; D006801:Humans; D051379:Mice; D008818:Mice, Neurologic Mutants; D009046:Motor Neurons / Q000473:pathology / Q000502:physiology*; D010641:Phenotype; D000090063:Proto-Oncogene Mas; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D019076:Transgenes
chemical_list: C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D019253:Proto-Oncogene Proteins c-bcl-2