A novel strategy for introducing exogenous bcl-2 into neuronal cells: the Cre/loxP system-mediated activation of bcl-2 for preventing programmed cell death using recombinant adenoviruses

Mol Cell Neurosci. 1998 Sep;12(1-2):65-78. doi: 10.1006/mcne.1998.0703.

Abstract

We have established a novel strategy for introducing exogenous Bcl-2 into neuronal cells that is mediated by Cre/loxP recombination using recombinant adenoviral vectors. An on/off-switching cassette for Bcl-2 (CALNLbcl-2) was designed to express Bcl-2 by recombinase Cre-mediated excisional deletion of a spacer DNA flanked by a pair of loxP sites. Exogenous Bcl-2 was clearly induced in PC12 cell lines carrying CALNLbcl-2 after infection with recombinant adenovirus producing recombinase Cre (AxCANCre). Dual infection with both AxCANCre and a recombinant adenovirus bearing CALNLbcl-2 showed efficient delivery of exogenous Bcl-2 into a hybrid motoneuronal cell line and primary chicken spinal motoneurons. The delivery of foreign Bcl-2 promoted survival of motoneurons in medium either containing or lacking trophic support. Thus, this strategy for delivery of exogenous Bcl-2 will be useful for studying neuronal death as well as for introducing foreign genes into postmitotic neurons under the control of recombinase Cre.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenoviridae Infections / genetics
  • Adenoviridae*
  • Animals
  • Apoptosis / physiology
  • Chick Embryo
  • DNA Replication
  • Gene Expression Regulation, Viral
  • Genes, Viral / physiology
  • Humans
  • Integrases / metabolism*
  • Kidney / cytology
  • Neurons / cytology*
  • Neurons / enzymology
  • Neurons / virology
  • PC12 Cells
  • Proto-Oncogene Proteins c-bcl-2 / genetics*
  • Rats
  • Recombinant Fusion Proteins / physiology
  • Transduction, Genetic*
  • Viral Proteins*

Substances

  • Proto-Oncogene Proteins c-bcl-2
  • Recombinant Fusion Proteins
  • Viral Proteins
  • Cre recombinase
  • Integrases