Dopamine B-hydroxylase (DBH) catalyzes the final step in the biosynthesis of norepinephrine, the principal classic neurotransmitter of peripheral sympathetic neurons. We have shown that 5.8 kb of 5’upstream region from a cloned human DBH gene promoter is sufficient to direct expression of the E. coli/acZ gene in transgenic mice to neurons of the locus ceruleus and other classic noradrenergic brain stem nuclei, sympathetic ganglion neurons, and adrenal chromaffin cells./acZ expression was also observed in neurons of the enteric system, the retina, some sensory and all cranial parasympathetic ganglia, and some diencephalic and telencephalic brain nuclei. The expression pattern of the transgene in DBH-immunonegative sites overlapped with many sites where expression of tyrosine hydroxylase or phenylethanolamine N-methyltransferase, two other catecholamine biosynthetic enzymes, has been reported. introduction

The sympathetic nervous system has a relatively simple structureand well-characterized functions, and its prripheralcomponentsareeasilyaccessibletoexperimental manipulation. This has made it one of the best-understood vertebrate neural systems and an excellent model for the more complex brain. The sympathetic nervous system plays diverse homeostatic roles, but many sympathetic components become particularly active in times of stress, resulting in increased heart rate, arterial vasotension, blood flow to the musculature, and suppression of gastrointestinal motility. In the periphery, its major constituents are the paravertebral sympatheticchain ganglia, prevertebral ganglia, and one neuroendocrine element-the adrenal medulla. These primarily catecholaminergic stuctures receive stimulatory input from cholinergic spinal intermediolateral column neurons, which in turn receive input from higher CNS centers(Strack et al., 1989a, 1989b). Peripheral sympathetic neurons project to the enteric nervous system and to various ultimate targets including arterial smooth muscle, salivary glands, sweat glands, and the heart, whereas