Baetge E E, Behringer R R, Messing A, Brinster R L, Palmiter R D
Howard Hughes Medical Institute, University of Washington, Seattle 98195.
Proc Natl Acad Sci U S A. 1988 May;85(10):3648-52. doi: 10.1073/pnas.85.10.3648.
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.
负责将去甲肾上腺素转化为肾上腺素的人苯乙醇胺N-甲基转移酶（hPNMT）基因已被克隆，其完整的核苷酸序列也已确定。该结构基因由三个外显子和两个内含子组成，跨度约为2100个碱基对。构建了含有带有2千碱基或8千碱基5'侧翼序列的hPNMT基因的转基因小鼠，结果在肾上腺和眼睛中表达了hPNMT mRNA。一个由2千碱基的hPNMT 5'侧翼区域与猿猴病毒40早期区域融合而成的嵌合基因，也导致肾上腺和眼睛中肿瘤（T）抗原mRNA的表达；此外，免疫细胞化学显示肿瘤抗原定位于肾上腺髓质细胞的细胞核和视网膜内核层细胞中，这些都是肾上腺素合成的主要部位。这些结果表明，在这些细胞类型中hPNMT基因适当表达的增强子位于人类基因的2千碱基5'侧翼区域。
