Neurotransmitter abnormality in Rolling mouse Nagoya, an ataxic mutant mouse.

An extensive neurochemical study has been performed on the CNS of Rolling mouse Nagoya (RMN), an ataxic mutant mouse. Although the symptoms observed are as severe as those found in Weaver mutants, little is known of the pathogenesis of the ataxia, except for a slight hypoplasia of the anterior part of the cerebellum. The present study revealed two major neurotransmitter-related abnormalities in the CNS. The first is a reduced concentration of glutamate, a putative transmitter of granule cells, and an increased concentration of glycine and taurine in the cerebellum of the RMN. The second is an increased activity of tyrosine hydroxylase, the rate-limiting enzyme in catecholamine synthesis, not only in the cerebellum but also in spinal cord, medulla oblongata, thalamus and hypothalamus. These results, together with previous data obtained from other ataxic mutant mice or experimentally-induced ataxic animals suggest that the cerebellum is the most severely affected part of the CNS in the RMN with the number of granule cells being reduced. The increase in the concentration of inhibitory amino acids and the widespread increase in tyrosine hydroxylase activity are probably not specific to the RMN but seem to be common to other ataxic animals with hypoplastic cerebellum and granule cell loss.