205. Functional Assessment of NSE-Cre Mouse Model of Friedreich Ataxia

Abstract

The characterization of mouse models of human disease is essential for understanding the underlying pathophysiology and developing new therapeutics. To understand more clearly the pathogenesis of sensorimotor dysfunction in Friedreich ataxia, we used conditional knockout mice in which the frataxin gene had been knocked-out in some tissues during embryogenesis by breeding them with mice expressing the Cre recombinase gene under the NSE promoter. The NSE-Cre mice grew poorly compared to their controls, and demonstrated a severe neurologic phenotype, and a shorter life span. They exhibited extended duration of the hindlimb clasping response, as well as slowed movement time on a suspended bar, severe ataxic gait and kyphosis. The mutants have poor somatosensory perception, breathing difficulties, heart palpitation and autonomic dysfunction as indicated by urogenital failure. Despite the short life span, the NSE-Cre mice are a valid model to evaluate behavioral deficits and could be used to test experimental therapies to improve functional responses.