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 approximately 14 kb. The largest intron (intron 8) is approximately 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 alpha 6 gene upstream region confers expression on a beta-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 beta-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 alpha 6 subunit gene and that confers neuron-specific expression.
Jones
A
A
MRC Laboratory of Molecular Biology, MRC Centre, Cambridge, England.
Bahn
S
S
Grant
A L
AL
Köhler
M
M
Wisden
W
W
D017398:Alternative Splicing / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D001345:Autoradiography; D001483:Base Sequence; D002531:Cerebellum / Q000166:cytology*; D002874:Chromosome Mapping; D005091:Exons / Q000235:genetics; D005786:Gene Expression Regulation / Q000502:physiology; D017403:In Situ Hybridization; D007438:Introns / Q000235:genetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009474:Neurons / Q000737:chemistry* / Q000502:physiology; D011401:Promoter Regions, Genetic / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000737:chemistry / Q000235:genetics*; D017422:Sequence Analysis, DNA; D014158:Transcription, Genetic / Q000235:genetics; D019076:Transgenes / Q000235:genetics
D011963:Receptors, GABA-A