Rolling Nagoya Mouse

Abstract

The natural mutant mouse rolling Nagoya has an uncoordinated gait and frequently displays sideways body rolls. The mutation underlying this autosomal recessively inherited severely ataxic motor phenotype is present in Cacna1a, the gene encoding the pore-forming α 1 subunit of Ca V 2.1 type voltage-gated Ca 2+ channels. This type of channel is crucially involved in neuronal Ca 2+ signaling and in neurotransmitter release from nerve terminals at many central synapses and, in the periphery, at the neuromuscular junction. This chapter reviews the phenotypic, motor behavioral, histological, biochemical, neurophysiological, and electrophysiological findings in this mouse mutant. Human neurological diseases exist which are associated with Ca V 2.1 dysfunction ("Ca 2+ -channelopathy"), either due to a CACNA1A mutation or an autoimmune attack of Ca V 2.1 channels. The relevance of the rolling Nagoya mouse mutant as a model for these diseases is discussed.