Characterization of a Cerebellar Granule Cell-Specific Gene Encoding the γ-Aminobutyric Acid Type A Receptor α6 Subunit

Authors


  • The promoter sequences reported have been deposited in the EMBL database with accession nos. X97475 (mouse) and X97476 (rat).

Address correspondence and reprint requests to Dr. W. Wisden at Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge, CB2 2QH, U.K.

Abstract

Abstract: The α6 subunit of γ-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 α6 subunit gene has nine exons and spans ∼14 kb. The largest intron (intron 8) is ∼7 kb. For a minority of mRNAs, a missplice of the 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 rat α6 gene upstream region confers expression on a β-galactosidase reporter gene. One founder gave rise to a line with cerebellar granule cell-specific expression, although expression varied with lobule region. Other founders had ectopic but neuron-specific expression, with β-galactosidase found in cerebellar Purkinje cells, neocortex, thalamus, hippocampus, caudate-putamen, and inferior colliculi. Thus, we have defined a region containing the basal promoter of the α6 subunit gene and that confers neuron-specific expression.

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