Genetic Models of Cerebellar Dysfunction

Mice with spontaneous mutations or with genetic modifications serve as models of spinocerebellar atrophy (SCA) and Friedreich’s ataxia. ATXN1 , ATXN2 , ATXN3 , and ATXN7 transgenic mice mimic SCA1, SCA2, SCA3, and SCA7, respectively, while Spnb3 and Atxn8os null mutants mimic SCA5 and SCA8, respectively, with age-related onset of cerebellar pathology and motor-coordination deficits. The onset in spontaneous mutations generally occurs prior to or during the weaning period, providing information on the consequences of cerebellar lesions throughout the animal’s lifetime. Prevalent tests to screen cerebellar dysfunction include the stationary beam, suspended wire, inclined grid, rotorod, exploratory activity, and spatial orientation. Cartographies of regional metabolism and neurotransmitter uptake sites and receptors provide valuable insight into the functional impact of cerebellar lesions throughout the brain and their relation with behavioral deficits, to facilitate pharmacotherapies aimed at mitigating symptoms of cerebellar-�related degenerative diseases.