Flies expressing ND75GD6309 under the control of Scer\GAL4da.PU exhibit progressive neurodegeneration: no neuron loss is seen at one day, but significant cortical neuron loss is observed at 10 days old. An increased amount of cell death (caspase activation) is seen compared to controls, and the majority of these cells are neurons rather than glia. The mitochondria of cortical cells are enlarged compared to controls, and both neurons and glia are affected. At 30 days, the number and size of the mitochondria is dramatically increased, sometimes to the extent of almost filling the cytoplasm. Mitochondrial defects observed include honeycombing, effacement of cristae and concentric lamellations of the internal mitochondrial membrane.
When ND75GD6309 is expressed in neurons under the control of Scer\GAL4elav.PU no neuronal loss, vacuolation or mitochondrial enlargement is observed. However the lifespan of these flies is significantly shortened and climbing dysfunction is observed in five day old flies.
When ND75GD6309 is expressed in glia under the control of Scer\GAL4repo.PU neuronal loss, cortical vacuolation and diffuse mitochondrial enlargement are observed. Lifespan is reduced but not climbing defects are seen compared to controls.
Adults expressing ND-75GD6309 under the control of Scer\GAL4elav.PLu (in the presence of Dcr-2Scer\UAS.cDa to increase the efficiency of RNAi) show significantly reduced avoidance of noxious temperature (46[o]C) compared to control flies.