Ca2＋チャンネル病マウスにおける小脳の異常と運動失調

This review summarizes recent studies on the morphological abnormalities of cerebella in four ataxic mutant mice, i.e., tottering mouse, leaner mouse, rolling mouse Nagoya (RMN) and rocker mouse. These mutants carry mutations in the Ca2+ channel α1A subunit gene, and become useful models for human Ca2+ channelopathy such as episodic ataxia type-2 and familial hemiplegic migraine. Abnormal expression of tyrosine hydroxylase (TH) in some Purkinje cells has been observed in tottering mice, leaner mice and RMN, but not in rocker mice. However, Purkinje cells did not seem to synthesize catecholamines. Since the transcription of the TH gene is facilitated by Ca2+, TH expression in the mutant Purkinje cells indicates functional abnormality by alterations in intracellular Ca2+ concentrations. Corticotropin-releasing factor (CRF) immunoreactivity in some climbing or mossy fibers was higher in RMN than in controls. Double immunostaining for CRF and TH revealed a correspondence in the distribution of TH-positive Purkinje cells to terminal fields of CRF-positive climbing fibers in RMN. Therefore, CRF seems to alter granule and Purkinje cell functions, such as abnormal TH expression, indicating the possible expression of ataxic symptoms.