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Next Article 
Volume 16, Number 19,
Issue of October 1, 1996
pp. 5897-5904
Copyright ©1996 Society for Neuroscience
Bcl-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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