Purkinje cells and granule cells in the cerebellum of the Stumbler mutant mouse.

The lesion in a new neurologically mutant mouse, Stumbler, has been studied using a Golgi technique and electron microscopy. Heterozygote Stumbler mice have smaller cerebella than their normal littermates from the earliest age studied (9 days postnatal). Purkinje cells have small immature-looking dendritic trees and retain somatic spines for up to 14 days longer than in normal mice. The Purkinje cells in the mutant also exhibit dark-staining organelles in their cytoplasm, as shown by light microscopy. By electron microscopy these organelles have been identified as mitochondria. Profiles of mitochondria are more abundant in both the Purkinje cell somata and dendrites of Stumbler mice, when compared to the normal. Purkinje cells are reduced in number from the earliest age studied, although degenerating Purkinje cells are not seen before P21. At this age, some of the remaining Purkinje cells in Stumbler begin to look almost normal, both in gross morphology and internal structure. No obvious changes in morphology have been seen in the granule cells but the population is reduced in number from P10 onwards. Some granule cell degeneration has been found in the Stumbler cerebellum, but this also occurs in the normal mouse at the same time, and therefore this has not been considered abnormal. The lesion in the cerebellar cortex of this mutant mouse is discussed with respect to the lesions found in some other mutant mice with cerebellar defects.