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Establishing a role of Nurr1 in adult DA neurons by conditional gene ablation in the adult substantia nigra

We will investigate the function of the protein Nurr1 in the adult mouse brain. Nurr1 belongs to the family of steroid hormone receptors but lacks an identified ligand. We have previously shown that Nurr1 plays a critical role for the development of dopamine neurons. However, Nurr1 continues to be expressed also in dopamine neurons of the adult brain. Previous data have indicated that Nurr1 might be important for the survival of dopamine neurons in the adult brain and its function may be compromised in patients with Parkinson's disease. If this is the case, Nurr1 could be a potentially important drug target. In this project we will use so called floxed Nurr1 mice, a strain of mice that can be used to conditionally knock-out Nurr1 selectively in the adult dopamine neurons. The aim of the project is to conclusively establish the role of Nurr1 in the adult brain. The results should tell if Nurr1 is of interest as a potential drug target and we also hope that the experiments will help to establish a potentially important new pre-clinical model for dopamine neuron dysfunction.

Final Outcome

After overcoming technical issues, Drs. Bjorklund and Perlmann were able to establish models to examine the role of NURR1 in the adult nervous system. Phenotypes are still being characterized. MJFF is supporting these ongoing efforts.


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