Apoptotic cell death of cerebellar granule neurons in genetically ataxia (ax) mice.

An autosomal recessive neurological mutant, ataxia (ax) mouse, was investigated to determine whether neuronal cell death occurs in the brain. The brains of homozygotes (ax(J)/ax(J)) and phenotypically normal littermates (ax(J)/+ or +/+) aged at 23-38 days were examined by the terminal dUTP nick-end-labeling (TUNEL) method. A few TUNEL-positive cells were observed in the granule cell layer of the cerebellum, the dentate gyrus, and the olfactory bulb of normal mice. In the affected mice, the number of TUNEL-positive cells was significantly increased in the cerebellum, particularly in the granule cell layer, compared to normal littermates. The findings suggest that ax mice will be useful as a model for studies on the genetic basis of apoptotic neuronal cell death.