Attenuation of MPTP-induced neurotoxicity and behavioural impairment in NSE-XIAP transgenic mice
X-linked IAP protein is a potent inhibitor of cell death. Here, we describe a novel transgenic mouse in which the human XIAP gene is expressed under the control of the neuron-specific enolase promoter (NSE-xiap). We demonstrate that nigrostriatal dopamine neurons of NSE-xiap mice were resistant to the damaging effects of the dopaminergic neurotoxin MPTP. MPTP-induced reduction of striatal dopamine metabolism was also attenuated in NSE-xiap mice. Furthermore, NSE-xiap mice treated with MPTP did not exhibit deficits in exploratory behaviour in an open-field test. Taken together, these findings suggest that strategies to enhance neuronal expression of XIAP may provide therapeutic benefit for the treatment of neurodegeneration in Parkinson's disease.
|Journal||Neurobiology of Disease|
Crocker, S.J., Liston, P., Anisman, H, Lee, C.J., Smith, P, Earl, N., … Robertson, G.S. (2003). Attenuation of MPTP-induced neurotoxicity and behavioural impairment in NSE-XIAP transgenic mice. Neurobiology of Disease, 12(2), 150–161. doi:10.1016/S0969-9961(02)00020-7