DIRECTING GENE-EXPRESSION TO CEREBELLAR GRANULE CELLS USING GAMMA-AMINOBUTYRIC-ACID TYPE-A RECEPTOR ALPHA-6 SUBUNIT TRANSGENES

Expression of the gamma-aminobutyric acid type A receptor alpha 6 subu nit gene is restricted to differentiated granule cells of the cerebell um and cochlear nucleus. The mechanisms underlying this limited expres sion are unknown. Here we have characterized the expression of a serie s of alpha 6-based transgenes in adult mouse brain. A DNA fragment con taining a 1-kb portion upstream of the start site(s), together with ex ons 1-8, can direct high-level cerebellar granule cell-specific report er gene expression. Thus powerful granule cell-specific determinants r eside within the 5' half of the alpha 6 subunit gene body. This intron -containing transgene appears to lack the cochlear nucleus regulatory elements. It therefore provides a cassette to deliver gene products so lely to adult cerebellar granule cells.