Quantitative examination of the deep cerebellar nuclei in the staggerer mutant mouse

Quantitative morphological techniques have revealed several new aspects of the action of the Staggerer mutant gene. Staggerer is an autosomal recessive gene which causes ataxia and severe malformation of the cerebellar cortex in mice. The Purkinje cells of the cerebellar cortex are small, abnormal in morphology and reduced in numbers. The close synaptic and developmental relationship of Purkinje cells with the cells of the deep cerebellar nuclei (dcn) lead us to look for effects of the Staggerer mutation on the dcn neurons. The volume of the deep nuclear region is shrunken in Staggerer and there is a reduction in the volume of the white matter. These findings account for the reduced wet weights and protein concentration found by Roffler-Tarlov and Sidman. In contrast to the cells of the cortex, where 75% of the medium-to-large neurons are missing, the number of cells present in Staggerer dcn is identical to wild-type. The dcn neurons are not completely spared, however. Measurements of cross-sectional cell area revealed a 30% shrinkage of neurons in Staggerer dcn. The most likely interpretation of previous work and the current findings is that the Staggerer gene acts early in development but exerts its effects directly only on those derivatives of the ventricular zone in the roof of the fourth ventricle which are destined to become Purkinje and Golgi cells.