Independent patterns of transcription for the products of the rat cholinergic gene locus

The cholinergic phenotype requires the expression of the vesicular acetylch oline transporter and choline acetyltransferase proteins. Both genes are en coded at one chromosomal location called the cholinergic gene locus. We hav e identified by in situ hybridization histochemistry distinct patterns of t ranscription from the cholinergic gene locus in the subdivisions of the rat cholinergic nervous system. The vesicular acetylcholine transporter and choline acetyltransferase are c o-expressed in cholinergic neurons at all developmental stages in all major types of cholinergic neurons. The relative levels of vesicular acetylcholi ne transporter and choline acetyltransferase transcripts, however, change s ubstantially during development in the CNS. They also differ dramatically i n distinct subdivisions of the mature cholinergic nervous system, with vesi cular acetylcholine transporter mRNA expressed at high levels relative to c holine acetyltransferase mRNA in the peripheral nervous system. but at equi valent levels in the CNS. Expression of the R-exon, the presumptive first non-coding exon common to b oth the vesicular acetylcholine transporter and choline acetyltransferase, was not detectable at any developmental stage in any of the cholinergic neu ronal subtypes in the rat nervous system. Thus, in contrast to less complex metazoan organisms, production of the vesicular acetylcholine transporter and choline acetyltransferase via a common differentially spliced transcrip t does not seem to occur to a significant extent in the rat. We suggest that separate transcriptional start sites within the cholinergic gene locus control vesicular acetylcholine transporter and choline acetylt ransferase transcription. while additional elements are responsible for the specific transcriptional control of the entire locus in cholinergic versus non-cholinergic neurons. independent transcription of the vesicular acetyl choline transporter and choline acetyltransferase genes provides a mechanis m for regulating the relative expression of these two proteins to fine-tune acetylcholine quantal sire in different types of cholinergic neurons, both centrally and peripherally. (C) 2001 IBRO. Published by Elsevier Science L td. All rights reserved.