INCREASED APOB100 MESSENGER-RNA IN INBRED STRAINS OF MICE BY ESTROGENIS CAUSED BY DECREASED RNA EDITING PROTEIN MESSENGER-RNA

Estrogen administration to rats diminishes all apoproteins and lipopro teins from plasma. In contrast, some inbred strains of mice raise thei r plasma apoB and LDL levels by more than 2-fold (Srivastava et al 199 3, fur. J. Biochem. 216, 527-538). Further studies with 13 inbred stra ins of mice given 3 mu g beta-estradiol/g body weight/day for 5 consec utive days suggest that some mouse strains increased their apoB and LD L levels and some did not. To examine the mechanism of influence of ge netic factors on apoB regulation, two strains, C57L and C57BL, that in creased their VLDL- and LDL-cholesterol, and 2 strains, BALE and C3H, that did not, were chosen. Estrogen increased plasma apoB levels selec tively in the strains C57L and C57BL, termed as 'responders,' but did not change in SALE and C3H, termed as 'non-responders.' One of the mec hanisms for increased plasma apoB levels could be through increased pr oduction of apoB-containing particles. This possibility was investigat ed. ApoB and REPR mRNA were quantified by RNase protection assay, and apoB-100 mRNA by apoB mRNA editing assay. Hepatic apoB mRNA increased by 30% in 'non-responders,' but decreased by 20% in the 'responders.' However, apoB-100 mRNA increased relative to apoB-48 mRNA in all the 4 strains by 50%. The mRNA for RNA editing protein (REPR) decreased in all strains, suggesting that apoB-100 mRNA increased as a result of de creased apoB mRNA editing activity. These results suggest that:(a) mod ulation of apoB mRNA by estrogen was strain-specific;(b) increased apo B100 mRNA in inbred strains of mice were caused by decreased apo8 mRNA editing activity;and(c) the differences in the plasma apoB levels amo ng 'responder' and 'nonresponder' strains of mice occur through mechan isms other than the apoB mRNA editing. (C) 1995 Academic Press, Inc.