[Genetic conversion of neurotransmitter phenotype in transgenic mice]

Abstract

The mammalian central and sympathetic nervous systems contain three kinds of catecholaminergic neuron (dopamine, norepinephrine and epinephrine neurons). Adrenal medulla also consists of cells producing either norepinephrine or epinephrine as hormones. To switch of catecholamine phenotype in the nervous and endocrine systems, we generated a line of transgenic mice carrying a chimeric gene containing human phenylethanolamine N-methyltransferase (PNMT) cDNA fused to the 4-kb fragment of the human dopamine beta-hydroxylase (DBH) gene promoter. Analysis of transgenic mice indicated that the additional expression of human PNMT in norepinephrine-producing cells can convert these cells to the epinephrine phenotype, and suggested that norepinephrine-producing cells normally possess the fundamental machinery required for the synthesis of epinephrine except for the PNMT expression.