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Molecular Endocrinology Vol. 6, No. 11 1951-1960
doi:10.1210/me.6.11.1951
Copyright © 1992 by the Endocrine Society.
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Molecular Endocrinology, Vol 6, 1951-1960, Copyright © 1992 by Endocrine Society

ARTICLES

Alteration of neurotransmitter phenotype in noradrenergic neurons of transgenic mice

GG Cadd, GW Hoyle, CJ Quaife, B Marck, AM Matsumoto, RL Brinster and RD Palmiter
Howard Hughes Medical Institute, Department of Biochemistry, University of Washington, Seattle 98155.

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.




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