VISUALIZATION AND ABLATION OF PHENYLETHANOLAMINE N-METHYLTRANSFERASE PRODUCING CELLS IN TRANSGENIC MICE

We cloned and sequenced the mouse phenylethanolamine N-methyltransfera se (PNMT) gene which encodes the enzyme that catalyses the conversion of norepinephrine to epinephrine. The ability of various length sequen ces flanking the mouse or human PNMT genes to direct expression of rep orter genes in transgenic mice was examined. We show that 9 kb of 5' f lanking sequences from the cloned mouse PNMT gene can direct expressio n of the Escherichia coli P-galactosidase (lacZ) gene to predicted reg ions of the adrenal, eye and brain in the adult transgenic mouse. The transgene was also expressed during development, in the myelencephalon , adrenal medulla and dorsal root ganglia. PNMT-producing cells were a blated by expression of the diphtheria toxin (DT-A) gene driven by the human PNMT promoter, resulting in abnormalities in the adrenal medull a, eye and testis. The hPNMT(8kb)-DT-A line presents a model with whic h to examine the developmental ramifications of deletion of PNMT-produ cing cell populations from the adrenal medulla and retina.