APOLIPOPROTEIN-E GENE-EXPRESSION IN VARIOUS TISSUES OF MOUSE AND REGULATION BY ESTROGEN

Apolipoprotein (apo)E is associated with several classes of lipoprotei ns and serves as a ligand for the receptor mediated uptake of choleste rol-rich particles by hepatocytes and peripheral tissues. Variant form s of apo E is also associated with dyslipidemia and late-onset of Alzh eimer's Disease (AD). We report here expression of apoE in various mou se tissues, and regulation of apoE in liver, kidney, brain and testes by supraphysiological doses of estrogen. ApoE mRNA was quantified by R Nase protection assay and translatable apoE mRNA by in vitro translati on. As an internal control the levels of beta-actin mRNA were also qua ntified. Highest levels of apoE were expressed in liver (220-280 pg/mu g RNA) with negligible levels in small intestine. Brain expressed hig hest levels of total (35-40 pg/mu g RNA) and translatable apoE mRNA ne xt only to liver. Other tissues that expressed relatively higher level s of apoE were adrenals, testes and ovary. ApoE was also found to be e xpressed in heart, lung, kidney and spleen. Regulation of apoE gene ex pression by estrogen (3 mu g 17 beta-estradiol/g body weight/day for 5 consecutive days) was studied in liver, kidney, brain and testes of 4 mouse strains. Hepatic apoE mRNA did not change significantly in any of the mouse strains following estradiol administration. Of note was s ignificant increases in the levels of brain apoE mRNA in the strain C3 K. These studies demonstrate that estrogen regulates apoE gene express ion in a tissue-specific manner in mice, and increases in apoE mRNA in the brain by estrogen may have implications in late-onset of Alzheime r's Disease.