Abnormalities in cerebellar Purkinje cells in the novel ataxic mutant mouse, pogo

Abstract

The pogo mouse is a novel neurological mutant, which was discovered, in an inbred strain ( KJR/MsKist) derived from a Korean wild mouse. The pathological manifestations include difficulty in maintaining normal posture, failures of interlimb coordination and the inability to walk straight. The ataxia is first apparent from about 2 weeks of age and progresses throughout life. The mutation is inherited as an autosomal recessive trait. In this report, we describe abnormalities in the pogo/pogo cerebellum. Nissl staining shows that the pogo/pogo cerebellum is normal in size and lobulation. Similarly, immunocytochemical staining for a granule cell marker, 10B5, shows no differences in the thickness of the granular layer between pogo/pogo homozygote and pogo/+ heterozygote littermate controls. By using anti-parvalbumin immunocytochemistry, the cells of molecular layer of the pogo/pogo cerebellum also appeared similar in distribution as compared to normal wild type mouse. In anti-neurofilament immunocytochemistry, the basket cells axons of the pogo/pogo cerebellum appeared normal. Purkinje cell abnormalities were identified by using anti-calbindin D immunocytochemistry. In 120-day-old pogo/pogo mutant mice there was a loss of Purkinje cells throughout the cerebellar vermis. Furthermore, the somata and dendrites were extensively vacuolated in the pogo/pogo Purkinje cells and the primary dendrites were frequently swollen. Focal axonal swellings were commonly observed in the Purkinje cell axons of pogo/pogo mutant mice as they traversed the granular layer. These data suggest that the progressive ataxia seen in pogo mice may be due to a failure of normal Purkinje cell activity.