Voltage-dependent Calcium Channel (VDCC) alpha(1A) Subunit Expression in the Ataxic Mutant, Pogo Mice Cerebellum

Lee, Nam Seob; Kim, Chul Tae; Han, Seung Yun; Kim, Jin Seong; Kim, Jae Min; Son, Jin A; Jeong, Young Gil

Abstract

The pogo mouse is a new ataxic mutant derived from a Korean wild mouse. The pogo mutation is inherited as an autosomal recessive trait on chromosome 8. Mutations in gene coding for the alpha(1A)subunit of voltagegated P/Q-type Ca(2+) channel have been shown to cause phenotypes in humans and mice, i.e., tottering, leaner, rolling mouse mouse Nagoya. Using immunohistochemistry, the expression of the alpha(1A)subunit of voltage-gated P/Q-type Ca(2+) channel was examined in pogo mice cerebellum including deep cerebellar nuclei (DCN). We observed alpha(1A)immunoreactivity in the cerebellar cortex (Purkinje cell and granule cell) and DCN of ataxic pogo mice and heterozygote control mice. There was no difference in cerebellar cortical alpha(1A)immunoreactivity between ataxic pogo mice and heterozygous littermate controls (pogo/+). However, we observed alpha(1A)immunoreactivity in the Purkinje cells of control and ataxic pogo mice cerebellum and DCN. We found a significant difference between pogo and heterozygous controls in terms of alpha(1A)immunoreactivities in the DCN. alpha(1A)immunoreactivity in this nucleus in pogo was much higher than in heterozygous littermate controls. No significant differences were observed in the interposed nucleus between pogo and heterozygous controls, but we found that the alpha(1A)subunits were clearer and more abundant in the lateral and medial regions of pogo than in control mice in these regions, where only weak immunoreactivity was observed. This elevated expression of the alpha(1A)subunit in deep cerebellar neurons of pogo might be a compensation for the altered function of P/Q type calcium channel and be related with the induction of the ataxic phenotype in pogo mice.