PROMOTER ELEMENTS CONFERRING NEURON-SPECIFIC EXPRESSION OF THE BETA-2-SUBUNIT OF THE NEURONAL NICOTINIC ACETYLCHOLINE-RECEPTOR STUDIED IN-VITRO AND IN TRANSGENIC MICE

Several genes encoding subunits of the neuronal nicotinic acetylcholin e receptors have been cloned and regulatory elements involved in the t ranscription of the alpha 2 and alpha 7-subunit genes have been descri bed. Yet, the detailed mechanisms governing the neuron-specific transc ription and the spatio-temporal expression pattern of these genes rema in largely uninvestigated. The beta 2-subunit is the most widely expre ssed neuronal nicotinic receptor subunit in the nervous system. We hav e studied the structural and regulatory properties of the 5' sequence of this gene. A fragment of 1163 bp of upstream sequence is sufficient to drive the cell-specific transcription of a reporter gene in both t ransient transfection assays and in transgenic mice. Deletion analysis and site-directed mutagenesis of this promoter reveal two negative el ements and one positive element. The positively-acting sequence includ es one functional E-box. One of the repressor elements is located in t he transcribed region and is the NRSE/RE1 sequence already described i n promoters of neuronal genes. In this paper, we describe the neuron-s pecific promoter of the gene encoding the neuronal nicotinic acetylcho line receptor beta 2-subunit.