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Journal of Lipid Research, Vol 34, 893-903, Copyright © 1993 by Lipid Research, Inc.

ARTICLES

Genetic variation in mouse apolipoprotein A-IV expression is determined pre- and post-transcriptionally

K Reue, DA Purcell-Huynh, TH Leete, MH Doolittle, A Durstenfeld and AJ Lusis
Wadsworth VA Medical Center, Los Angeles, CA 90073.

Among inbred mouse strains there is a striking genetic variation in the levels of apolipoprotein A-IV (apoA-IV) mRNA in the liver, although intestinal mRNA levels vary only twofold in these strains. In the present study we have characterized the apoA-IV expression phenotypes in strains C57BL/6J and 129/J, and investigated the molecular basis for the genetic variation. We report that the two strains differ eight- to tenfold both in the levels of apoA-IV mRNA and in the rate of apoA-IV protein synthesis in liver. Presumably due to the increased synthetic rate, strain 129 exhibits a threefold higher concentration of apoA-IV protein in the circulation. mRNA synthesis and turnover studies indicate that both transcriptional and post-transcriptional events contribute to the genetic variation in steady state apoA-IV mRNA levels. An analysis of the levels of apoA-IV mRNA derived from 129 and C57BL/6 alleles 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 genetically distinct trans-acting factors.
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