THE MOTONEURON DEGENERATION IN THE WOBBLER MOUSE IS INDEPENDENT OF THE OVEREXPRESSION OF A BC12 TRANSGENE IN NEURONS

The wobbler mouse mutation, an autosomal recessive mutation, leads to motoneuron degeneration in early post-natal development. Transgenic mi ce in which neurons overexpress human bcl2 transgene have been generat ed: the overexpression of bcl2 reduces the neuron loss during naturall y occurring and experimentally-induced cell deaths. In the present stu dy, we generate mice co-expressing the wobbler mutant gene and the bcl 2 transgene in order to determine the effects of Bcl2 overexpression o n the neurodegenerative disorders of the wobbler mouse. The clinical s igns of the disease (weakness, tremor, small size) as well as biochemi cal and histological parameters (choline acetyltransferase (ChAT) acti vity in muscles, gliosis in spinal cord) are similar in bcl2 positive and negative wobbler mice. These results point to the fact that the ne uron-specific expression of the human bcl2 transgene does not correct the effects of the wobbler mutation.