Cerebellar nitric oxide synthase, cGMP and motor function in two lines of cerebellar mutant mice, Staggerer and Wriggle Mouse Sagami.

We investigated the hypothesis that nitric oxide (NO) is involved in the cerebellar motor function, by measuring nitric oxide synthase (NOS) activities and cGMP in the cerebellum using two lines of mutant mice having motor dysfunction, Staggerer (SG) and Wriggle Mouse Sagami (WMS). In SG, the NOS activity per cerebellum was reduced to 5.8% of that of the controls, while no significant change was observed in WMS. The cerebellar cGMP in SG was reduced to 3.3% of that of the controls and to 43% in WMS. In contrast with these neurochemical markers of NO, the locomotor dysfunction and the number of falls were greater in WMS than in SG. The reductions of the neurochemical markers of NO are consistent with the results of the previous neuropathological studies in SG and WMS whereas the cerebellar motor dysfunction was independent of these neurochemical and neuropathological changes.