Genetic variation in mouse apolipoprotein A-IV expression is determined pre- and post-transcriptionally.
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.
Reue
K
K
Wadsworth VA Medical Center, Los Angeles, CA 90073.
Purcell-Huynh
D A
DA
Leete
T H
TH
Doolittle
M H
MH
Durstenfeld
A
A
Lusis
A J
AJ
D000818:Animals; D001054:Apolipoproteins A / Q000096:biosynthesis* / Q000235:genetics; D001483:Base Sequence; D005260:Female; D005786:Gene Expression Regulation; D014644:Genetic Variation; D008099:Liver / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010641:Phenotype; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000378:metabolism*; D013997:Time Factors; D014158:Transcription, Genetic
D001054:Apolipoproteins A; D012333:RNA, Messenger; C022205:apolipoprotein A-IV