ANTI-NUCLEAR ANTIBODIES RELATED TO ACETYLATOR PHENOTYPE IN MICE

  • 1 January 1980
    • journal article
    • research article
    • Vol. 213  (3) , 485-490
Abstract
A/J mice have been proposed as a model of the human systemic lupus erythematosus diathesis some workers have previously determined that they express a slow phenotype. Other workers showed A/J mice to have a predisposition to develop spontaneous and drug-induced antinuclear antibodies. A/J mice were mated with C57BL/6J mice, a rapid acetylator phenotype which is relatively resistant to spontaneous and drug-induced antinuclear antibodies, to assess the importance of flow acetylator status as a component of the lupus diathesis. Procainamide, a potent inducer of antinuclear antibodies, was acetylated to a lesser degree by A/J mice than by C57BL/6J mice. This difference, detectable by in vitro assay but not by urinary levels of acetylated drug, represents a genetic polymorphism which can be detected in F2 and backcross progency of these 2 strains. A/J mice had a higher incidence of spontaneous antinuclear antibodies than C56BL/6J mice and these antibodies can be induced in A/J mice by oral procainamide (6 g/l of drinking water for 37 wk); procainamide tended to suppress antinuclear antibody formation in C57BL/6J mice. Rapid and slow acetylators among F2 and backcross populations were identified by a test for N-acetyltransferase activity in blood hemolysates. These 2 groups together with their respective rapid and slow acetylator parents were compared in respect to incidence of antinuclear antibodies. Slow acetylator phenotypes among F2 and backcross mice were predisposed to high titers of antinuclear antibodies like the slow acetylator A/J strain. Long-term exposure to procainamide suppressed antinuclear antibody formation as was found in the rapid acetylator C57BL/6J strain. The ability to N-acetylate procainamide is not the sole factor controlling the ability of this drug to induce antinuclear antibodies.

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