Reue K, Purcell-Huynh D A, Leete T H, Doolittle M H, Durstenfeld A, Lusis A J
Wadsworth VA Medical Center, Los Angeles, CA 90073.
J Lipid Res. 1993 Jun;34(6):893-903.
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.
在近交系小鼠品系中，肝脏中载脂蛋白A-IV（apoA-IV）mRNA水平存在显著的遗传变异，尽管这些品系中肠道mRNA水平仅相差两倍。在本研究中，我们对C57BL/6J和129/J品系中的apoA-IV表达表型进行了表征，并研究了这种遗传变异的分子基础。我们报告说，这两个品系在肝脏中apoA-IV mRNA水平和apoA-IV蛋白质合成速率方面相差八到十倍。据推测，由于合成速率增加，129品系循环中apoA-IV蛋白质浓度高出三倍。mRNA合成和周转研究表明，转录和转录后事件均导致apoA-IV mRNA稳态水平的遗传变异。对F1小鼠中源自129和C57BL/6等位基因的apoA-IV mRNA水平的分析表明，apoA-IV mRNA水平的遗传控制涉及与apoA-IV基因相关的顺式作用元件以及遗传上不同的反式作用因子。
