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Adenovirus-Mediated Gene Transfer of the Tumor Suppressor, p53, Induces Apoptosis in Postmitotic Neurons
The Journal of Cell Biology (1996)
  • R. S. Slack, McGill University
  • Daniel Belliveau, The University of Western Ontario
  • M. Rosenberg, McGill University
  • J. Atwal, McGill University
  • H. Lochmuller, McGill University
  • R. Aloyz, McGill University
  • A. Haghighi, McGill University
  • B. Lach, University of Ottawa
  • P. Seth
  • E. Cooper, McGill University
  • F. D. Miller, McGill University
Programmed cell death is an ongoing process in both the developing and the mature nervous system. The tumor suppressor gene, p53, can induce apoptosis in a number of different cell types. Recently, the enhanced expression of p53 has been observed during acute neurological disease. To determine whether p53 overexpression could influence neuronal survival, we used a recombinant adenovirus vector carrying wild type p53 to transduce postmitotic neurons. A control consisting of the same adenovirus vector background but carrying the lacZ reporter expression cassette was used to establish working parameters for the effective genetic manipulation of sympathetic neurons. We have found that recombinant adenovirus can be used at titers sufficiently high (10 to 50 multiplicity of infection) to transduce the majority of the neuronal population without perturbing survival, electrophysiological function, or cytoarchitecture. Moreover, we demonstrate that overexpression of wild type p53 is sufficient to induce programmed cell death in neurons. The observation that p53 is capable of inducing apoptosis in postmitotic neurons has major implications for the mechanisms of cell death in the traumatized mature nervous system.
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Citation Information
R. S. Slack, Daniel Belliveau, M. Rosenberg, J. Atwal, et al.. "Adenovirus-Mediated Gene Transfer of the Tumor Suppressor, p53, Induces Apoptosis in Postmitotic Neurons" The Journal of Cell Biology Vol. 135 Iss. 4 (1996)
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