Cadd G G, Hoyle G W, Quaife C J, Marck B, Matsumoto A M, Brinster R L, Palmiter R D
Howard Hughes Medical Institute, Department of Biochemistry, University of Washington, Seattle 98155.
Mol Endocrinol. 1992 Nov;6(11):1951-60. doi: 10.1210/mend.6.11.1480181.
The normal complement of neurotransmitters in noradrenergic neurons was altered by expressing the structural gene for the enzyme phenylethanolamine-N-methyltransferase (PNMT) under the control of the dopamine-beta-hydroxylase gene promoter in transgenic mice. This resulted in accumulation of large amounts of epinephrine in neurons of the sympathetic nervous system (SNS) and central nervous system (CNS) but did not reduce norepinephrine levels. Adrenalectomy reduced PNMT levels in the SNS and CNS, suggesting that the transgene is positively regulated by adrenal steroids. Epinephrine levels were unaffected by this treatment in the CNS, suggesting that PNMT is not rate limiting for epinephrine synthesis. However, catecholamines were elevated in a sympathetic ganglion and a target tissue of the SNS, perhaps due to up-regulation of tyrosine hydroxylase in response to adrenalectomy. These transgenic mice also reveal a marked difference in the ability of chromaffin cells and neurons to synthesize epinephrine.
通过在转基因小鼠中，在多巴胺-β-羟化酶基因启动子的控制下表达苯乙醇胺-N-甲基转移酶（PNMT）的结构基因，去甲肾上腺素能神经元中神经递质的正常组成发生了改变。这导致交感神经系统（SNS）和中枢神经系统（CNS）的神经元中大量肾上腺素积累，但并未降低去甲肾上腺素水平。肾上腺切除术降低了SNS和CNS中的PNMT水平，表明转基因受到肾上腺类固醇的正向调节。肾上腺素水平在CNS中不受此处理的影响，表明PNMT不是肾上腺素合成的限速因素。然而，在交感神经节和SNS的靶组织中儿茶酚胺升高，这可能是由于肾上腺切除术后酪氨酸羟化酶上调所致。这些转基因小鼠还揭示了嗜铬细胞和神经元合成肾上腺素能力的显著差异。
