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2009 | 69 | 1 | 138-145

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Striking pattern of Purkinje cell loss in cerebellum of an ataxic mutant mouse, tottering

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Tottering mouse is an ataxic mutant that carries a mutation in a gene encoding for the ?1A subunit of P/Q-type Ca2+ channel (Cav2.1). This study revisited to examine whether a Purkinje cell loss occurred in the cerebellum of tottering mice. In tottering mice, Calbindin D-28k negative gaps were apparent in the vermis but not in the hemisphere. Calbindin D-28k immunofluorescence with DAPI staining demonstrated the absence of Purkinje cells in the Calbindin D-28k negative gaps. The Purkinje cell loss seemed to be observed prominently in the zebrin II negative compartments of the anterior vermis, but in the zebrin II positive compartments of the posterior vermis. Quite consistent with the histopathological observations, quantitation of the density of Calbindin D-28k and zebrin II immunopositive Purkinje cells in the tottering cerebellum revealed that the Purkinje cells were selectively lost in the zebrin II immunonegative compartments of the lobules I and II but in the zebrin II immunopositive compartments in the lobule IX. Those results predict that the susceptibility to the Cav2.1 gene defect is different among Purkinje cell phenotypes of the tottering cerebellum rather than the expression pattern of mutated Cav2.1 channels. This may result in the reproducible parasagittal pattern of Purkinje cell loss.




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Kazuhiko Sawada, Department of Anatomy and Developmental Neurobiology, University of Tokushima Graduate School Institute of Health Biosciences, Tokushima, Japan


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