TRANSGENIC MICE EXPRESSING THE INTRACELLULAR DOMAIN OF THE P75 NEUROTROPHIN RECEPTOR UNDERGO NEURONAL APOPTOSIS

We have asked whether p75(NTR) may play a role in neuronal apoptosis b y producing transgenic mice that express the p75(NTR) intracellular do main within peripheral and central neurons, These animals showed profo und reductions in numbers of sympathetic and peripheral sensory neuron s as well as cell loss in the neocortex, where there is normally littl e or no p75(NTR) expression. Developmental loss of facial motor neuron s was not observed, but induced expression of the p75(NTR) intracellul ar domain within adult animals led to increased motor neuron death aft er axotomy, Biochemical analyses suggest that these effects were not a ttributable to a p75(NTR)-dependent reduction in trk activation but in stead indicate that the p75 NIR intracellular domain may act as a cons titutive activator of signaling cascades that regulate apoptosis in bo th peripheral and central neurons.