title: Genetic variation in mouse apolipoprotein A-IV expression is determined pre- and post-transcriptionally.
abstract: 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.
authors.affiliation: Wadsworth VA Medical Center, Los Angeles, CA 90073.
authors.forename: K
authors.initials: K
authors.lastname: Reue
authors.forename: D A
authors.initials: DA
authors.lastname: Purcell-Huynh
authors.forename: T H
authors.initials: TH
authors.lastname: Leete
authors.forename: M H
authors.initials: MH
authors.lastname: Doolittle
authors.forename: A
authors.initials: A
authors.lastname: Durstenfeld
authors.forename: A J
authors.initials: AJ
authors.lastname: Lusis
mesh_terms: 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
chemical_list: D001054:Apolipoproteins A; D012333:RNA, Messenger; C022205:apolipoprotein A-IV