GENETIC-VARIATION IN MOUSE APOLIPOPROTEIN A-IV EXPRESSION IS DETERMINED PRETRANSCRIPTIONALLY AND POSTTRANSCRIPTIONALLY

Among inbred mouse strains there is a striking genetic variation in th e levels of apolipoprotein A-IV (apoA-IV) mRNA in the liver, although intestinal mRNA levels vary only twofold in these strains. In the pres ent study we have characterized the apoA-IV expression phenotypes in s trains C57BL/6J and 129/J, and investigated the molecular basis for th e genetic variation. We report that the two strains differ eight- to t enfold both in the levels of apoA-IV mRNA and in the rate of apoA-IV p rotein synthesis in liver. Presumably due to the increased synthetic r ate, strain 129 exhibits a threefold higher concentration of apoA-IV p rotein in the circulation. mRNA synthesis and turnover studies indicat e that both transcriptional and post-transcriptional events contribute to the genetic variation in steady state apoA-IV mRNA levels. An anal ysis of the levels of apoA-IV mRNA derived from 129 and C57BL/6 allele s in F1 mice indicates that the genetic control of apoA-IV mRNA levels involves both cis-acting elements linked to the apoA-IV gene, and gen etically distinct trans-acting factors.