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Volume 16, Number 19, Issue of October 1, 1996 pp. 5897-5904
Copyright ©1996 Society for NeuroscienceBcl-2 Sensitivity Differentiates Two Pathways for Motoneuronal Death in the wobbler Mutant Mouse
Received Feb. 12, 1996; revised July 1, 1996; accepted July 9, 1996.
Muriel Coulpier, Marie-Pierre Junier, Marc Peschanski, and Patrick A. Dreyfus Institut National de la Santé et de la Recherche Médicale U421, 94010 Créteil Cedex, France
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.
Key words: wobbler; Bcl-2; developmental neuronal death; axotomy-induced cell death; excitotoxicity; neurotrophic factors
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