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Genetically Controlled Alterations in the Rate of Degradation of Phenylethanolamine N-Methyltransferase

From the ¹ From the Laboratory of Clinical Science, National Institute of Mental Health, Bethesda, Maryland 20014

Differences in phenylethanolamine N-methyltransferase (EC 2.1.1) between sublines of the Balb/c inbred mouse strain were examined. The adrenal glands of the Balb/cJ strain possessed nearly twice as much enzyme activity as the glands of the Balb/cN line. This difference was reflected in the adrenal gland content of the enzyme, since it took nearly twice as much anti-phenylethanolamine N-methyltransferase antiserum to precipitate the enzyme from the Balb/cJ line. Analysis of F₁ and F₂ progeny of the mating between Balb/cJ and Balb/cN lines revealed the enzyme levels to be controlled by a single genetic locus. Turnover studies showed the rates of phenylethanolamine N-methyltransferase synthesis to be the same in the two mouse sublines, but that the enzyme in the Balb/cN line was degraded at a rate twice that of the enzyme in the Balb/cJ line. Phenylethanolamine N-methyltransferase from both sublines was similar with respect to substrate affinities, thermal stability, tryptic stability, and electrophoretic mobility. On the basis of these studies, it is postulated that a single gene locus has mutated in one of these strains and that this mutation resulted in the altered degradation rate of the enzyme.

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