CELL-SPECIFIC EXPRESSION FROM THE HUMAN DOPAMINE-BETA-HYDROXYLASE PROMOTER IN TRANSGENIC MICE IS CONTROLLED VIA A COMBINATION OF POSITIVE AND NEGATIVE REGULATORY ELEMENTS

The promoter region of the human dopamine beta-hydroxylase (DBH) gene was analyzed in transgenic mice to identify DNA sequences responsible for the tissue- and cell-specific expression of the gene. Transgenic m ice were generated that carried the Escherichia coil lacZ gene under c ontrol of DBH promoter fragments between 0.6 and 5.8 kilobases (kb) in length. Sequences required for expression in adult and fetal noradren ergic neurons were located between 0.6 and 1.1 kb 5' to the DBH transc riptional start site. Sequences in this region and farther upstream al so directed expression to dopaminergic and noncatecholaminergic brain neurons that was repressed by negative elements elsewhere in the gene. The results indicate that the neuron-specific expression of the DBH g ene is mediated by positive regulatory elements but that negative elem ents are required to restrict expression to the proper subset of neuro ns.