CNTF OVERPRODUCTION HASTENS ONSET OF SYMPTOMS IN MOTOR-NEURON DEGENERATION (MND) MICE

Ciliary neurotrophic factor (CNTF) promotes the survival of motor neur ons, in vitro and in vivo. Moreover, CNTF can block the degeneration o f injured or diseased motor neurons in young rodents. Motor neuron deg eneration(mnd) mutant mice display adult onset symptoms reflecting pro gressive motor debilitation and provide a model in which to test the h ypothesis that CNTF can prevent the loss of these motor functions. We generated mnd mice that harbor a genomically integrated transgene, res ulting in overexpression of the encoded CNTF protein in these mice. In contrast to the beneficial effects of CNTF in preventing motor neuron degeneration in other experimental paradigms, we report that overprod uction of CNTF increased the rate of onset of motor disease symptoms i n mnd mice and the presence of the transgene correlated with low adult body weight in mnd and wild-type genetic backgrounds. (C) 1996 John W iley & Sons, Inc.