Distribution and characterization of the GABA receptors in the CNS of ataxic mutant mouse.

In an attempt to elucidate molecular pathogenesis of ataxia without cytological abberations in the cerebellum, Rolling Mouse Nagoya (C3Hf/Nem-rol) was used to study distribution of GABA receptors in membrane fractions. Among muscimol binding sites of various regions in the ataxic CNS, those in pons and medulla were significantly decreased (P less than 0.001) compared with control and non-ataxic heterozygote CNS, followed by cerebellum at a lower degree of significance (P less than 0.01). The kinetic studies demonstrated that dissociation constants of high- and low-affinity binding sites of muscimol of each control and those of ataxic mutant mouse were similar, i.e., KH = 41 nM and KL = 1.1 microM, respectively. GAD in the various regions was assayed, and it showed higher activity in the thalamus and hypothalamus, and lower activity in the cerebellum, of the ataxic mutant mouse as compared to that of the control mouse.