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The FASEB Journal • FJ Express Full-Length Article Dopamine enhances motor and neuropathological consequences of polyglutamine expanded huntingtin

By Michel Cyr, Tatyana D. Sotnikova, Raul R. Gainetdinov and Marc G. Caron


ABSTRACT An expansion in the CAG repeat of the IT15 (huntingtin) gene underlies the development of Huntington’s disease (HD), but the basis for the specific vulnerability of dopamine-receptive striatal neurons remains unclear. To examine the potential role of the dopamine system in the emergence of pathological conditions in HD, we generated a double mutant mouse strain with both enhanced dopamine transmission and endogenous expression of a mutant huntingtin gene. This strain was generated by crossing the dopamine transporter knock-out mouse, which exhibits a 5-fold elevation in extracellular dopamine levels in the striatum and locomotor hyperactivity, to a knock-in mouse model of HD containing 92 CAG repeats. These double mutant mice exhibited an increased stereotypic activit

Year: 2013
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