CHARACTERIZATION OF A CEREBELLAR GRANULE CELL-SPECIFIC GENE ENCODING THE GAMMA-AMINOBUTYRIC-ACID TYPE-A RECEPTOR ALPHA-6 SUBUNIT

The alpha 6 subunit of gamma-aminobutyric type A receptors is a marker for cerebellar granule cells and is an attractive candidate to study cell-specific gene expression in the brain. The mouse alpha 6 subunit gene has nine exons and spans similar to 14 kb, The largest intron (in tron 8) is similar to 7 kb. For a minority of mRNAs, a missplice of th e first exon was identified that disrupts the signal peptide and most likely results in the production of nonfunctional protein. The gene is transcribed from a TATA-less promoter that uses multiple start sites. Using transgenic mice, it was found that the proximal 0.5 kb of the r at alpha 6 gene upstream region confers expression on a beta-galactosi dase reporter gene. One founder gave rise to a line with cerebellar gr anule cell-specific expression, although expression varied with lobule region. Other founders had ectopic but neuron-specific expression, wi th beta-galactosidase found in cerebellar Purkinje cells, neocortex, t halamus, hippocampus, caudate-putamen, and inferior colliculi, Thus, w e have defined a region containing the basal promoter of the alpha 6 s ubunit gene and that confers neuron-specific expression.