Transgenic mice express the human phenylethanolamine N-methyltransferase gene in adrenal medulla and retina.
The human gene for phenylethanolamine N-methyltransferase (hPNMT), responsible for the conversion of norepinephrine to epinephrine, has been cloned and the complete nucleotide sequence has been determined. The structural gene consists of three exons and two introns spanning approximately equal to 2100 base pairs. Transgenic mice containing the hPNMT gene with either 2 or 8 kilobases of 5'-flanking sequence were produced and resulted in expression of hPNMT mRNA in the adrenal gland and eye. A chimeric gene consisting of 2 kilobases of the hPNMT 5'-flanking region fused to the simian virus 40 early region also resulted in tumor (T) antigen mRNA expression in adrenal glands and eyes; furthermore, immunocytochemistry showed that tumor antigen was localized in nuclei of adrenal medullary cells and cells of the inner nuclear cell layer of the retina, prominent sites of epinephrine synthesis. These results indicate that the enhancer(s) for appropriate expression of the hPNMT gene in these cell types is in the 2-kilobase 5'-flanking region of the human gene.
Baetge
E E
EE
Howard Hughes Medical Institute, University of Washington, Seattle 98195.
Behringer
R R
RR
Messing
A
A
Brinster
R L
RL
Palmiter
R D
RD
D000313:Adrenal Medulla / Q000201:enzymology*; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D004262:DNA Restriction Enzymes; D005796:Genes; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009693:Nucleic Acid Hybridization; D010625:Phenylethanolamine N-Methyltransferase / Q000235:genetics*; D012160:Retina / Q000201:enzymology*
D010625:Phenylethanolamine N-Methyltransferase; D004262:DNA Restriction Enzymes