Ectopic expression of tyrosine hydroxylase in Zebrin II immunoreactive Purkinje cells in the cerebellum of the ataxic mutant mouse, pogo

Abstract

The pogo mouse is a new ataxic autosomal recessive mutant that arose in an inbred strain ( KJR/MsKist) derived from a Korean wild mouse. The phenotype includes difficulty in maintaining normal posture and the inability to walk straight. Several previous studies have associated inherited ataxia with the ectopic expression of tyrosine hydroxylase (TH) in Purkinje cells. Therefore, in the present study, the distribution of TH expression was compared with that of zebrin II in Purkinje cells of adult pogo/pogo mutant mice. In normal control littermates, tyrosine hydroxylase immunoreactivity is confined to a delicate axonal plexus ramifying through the molecular layer. In pogo/pogo, in addition to the axonal plexus, TH-immunoreactive Purkinje cells were present in all lobules of the cerebellar vermis and hemispheres, distributed as series parasagittal bands. The general pattern of expression is reproducible between individuals and symmetrical about the midline. Alternating stripes of TH expression are also seen in the hemispheres, and most Purkinje cells in the paraflocculi and flocculi are immunoreactive. In pogo/+ mice, TH-immunoreactive Purkinje cells are rare. The pattern of zebrin II expression was used to map TH immunoreactive Purkinje cells in pogo/pogo mutant mice. Double immunofluorescence labeling combining anti-zebrin II fand anti-TH showed that all TH-immunoreactive Purkinje cells are zebrin II+, but that many zebrin II+ Purkinje cells within a band do not stain with anti-TH. Taken together with the morphological changes observed in the Purkinje cell axons, this suggests that abnormal Purkinje cell function may contribute to the ataxic phenotype in pogo/pogo mice.