ISSN:
1471-4159
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
Abstract : Choline acetyltransferase (ChAT) is a specific phenotypicmarker of cholinergic neurons. Previous reports showed that different upstreamregions of the ChAT gene are necessary for cell type-specific expression ofreporter genes in cholinergic cell lines. The identity of the mouse ChATpromoter region controlling the establishment, maintenance, and plasticity ofthe cholinergic phenotype in vivo is not known. We characterized a promoterregion of the mouse ChAT gene in transgenic mice, using β-galactosidase(LacZ) as a reporter gene. A 3,402-bp segment from the5′-untranslated region of the mouse ChAT gene (from -3,356 to +46, +1being the translation initiation site) was sufficient to direct the expressionof LacZ to selected neurons of the nervous system ; however, it didnot provide complete cholinergic specificity. A larger fragment (6,417 bp,from -6,371 to +46) of this region contains the requisite regulatory elementsthat restrict expression of the LacZ reporter gene only in cholinergic neurons of transgenic mice. This 6.4-kb DNA fragment encompasses 633 bp of the 5′-flanking region of the mouse vesicular acetylcholine transporter (VAChT), the entire open reading frame of the VAChT gene, contained within the first intron of the ChAT gene, and sequences upstream of the start coding sequences of the ChAT gene. This promoter will allow targeting of specific gene products to cholinergic neurons to evaluate the mechanisms of diseases characterized by dysfunction of cholinergic neurons and will be valuable in design strategies to correct those disorders.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1046/j.1471-4159.1999.0720017.x
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