Chromosomal localization and neural distribution of voltage dependent calcium channel alpha1A and alpha1E subunit genes / 대한해부학회지

ABSTRACT

Fluorescent in situ hybridization using human genomic DNA probes was performed to localize genes encoding the alpha1A and alpha1E of voltage dependent calcium channels (VDCCs) in the human chromosome and the mRNA expression of these two alpha1 subunits of VDCC was demonstrated in the 18 day old embryo (E18) and adult rat brain by in situ hybridization histochemistry. The genes for the VDCC alpha1A and alpha1E were specifically localized on human chromosome 19p13.1 and 1q25, respectively. In 18 days old rat embryos, the mRNAs of the VDCC alpha1A and alpha1E were predominently expressed in the nervous system including brain and spinal cord. In adult rat brain, the expression pattern of each subunit was extremely different. The expression of alpha1A mRNA was strong in the purkinje cells of cerebellum and CA3 area of hippocampus, relatively high level of expression was found in the dentate gyrus, CA1 area of hippocampus, superficial layer of cerebral cortex and olfactory mitral cells. Whereas alpha1E was highly expressed in the dentate gyrus, CA1-3 area of hippocampus, medial habenula nucleus of thalamus and olfactory mitral and internal granule cells and relatively high level of expression was found in the Purkinje cells of cerebellum, cerebral cortex and caudate-putamen. Until now, no neurological disorder has been mapped to 1q25, location of VDCC alpha1E gene. Recently, it has been reported that mutation of VDCC alpha1A gene causes episodic ataxia type 2 (EA-2) and spinocerebellar ataxia 6 (SCA6). These reports comfirm the our experimental results of chromosomal mapping and prominent cerebellar expression of VDCC a1A gene.