BCL-2 TRANSGENE EXPRESSION CAN PROTECT NEURONS AGAINST DEVELOPMENTAL AND INDUCED CELL-DEATH

The bcl-2 protooncogene, which protects various cell types from apopto tic cell death, is expressed in the developing and adult nervous syste m. To explore its role in regulation of neuronal cell death, we genera ted transgenic mice expressing Bcl-2 under the control of the neuron-s pecific enolase promoter, which forced expression uniquely in neurons. Sensory neurons isolated from dorsal root ganglia of newborn mice nor mally require nerve growth factor for their survival in culture, but t hose from the beta transgenic mice showed enhanced survival in its abs ence. Furthermore, apoptotic death of motor neurons after axotomy of t he sciatic nerve was inhibited in these mice, The number of neurons in two neuronal populations from the central and peripheral nervous syst em was increased by 30%, indicating that Bcl-2 expression can protect neurons from cell death during development. The generation of these tr ansgenic mice suggests that Bcl-2 may play an important role in surviv al of neurons both during development and throughout adult life.