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. 1986 Nov;6(11):3807–3814. doi: 10.1128/mcb.6.11.3807

Mouse apolipoprotein A-IV gene: nucleotide sequence and induction by a high-lipid diet.

S C Williams, S M Bruckheimer, A J Lusis, R C LeBoeuf, A J Kinniburgh
PMCID: PMC367142  PMID: 3796595

Abstract

Apolipoprotein A-IV (apo A-IV) functions in conjunction with other apolipoproteins to form lipoprotein particles which are involved in lipid homeostasis. In this report we present the nucleotide sequence of the mouse apo A-IV gene and demonstrate its induction in the liver by chronically high dietary lipid. The apo A-IV gene consists of three exons and two introns. The introns separate evolutionarily conserved and functional polypeptide domains. Intron 1 divides most of the apo A-IV signal peptide from the amino terminus of the mature plasma protein. The second intron separates a highly evolutionarily conserved, variant amphipathic peptide repeat from the remainder of the mature apo A-IV protein. The 5' flanking region has several interesting features. The apo A-IV gene has variant TATA and CAT box sequences, TTTAAA and CCAACG, respectively. There are five G-rich direct repeats of 10 nucleotides and a short inverted repeat in the 5' flanking region. We speculate that these sequence elements in the 5' flanking region may be involved in the regulation of apo A-IV gene expression. We also show that chronically high dietary lipid induces liver apo A-IV levels 10-fold in C57BL/6 mice, a strain susceptible to atherosclerotic lesions, while we observed no induction in nonsusceptible BALB/c and C3H mice.

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Selected References

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  1. Benton W. D., Davis R. W. Screening lambdagt recombinant clones by hybridization to single plaques in situ. Science. 1977 Apr 8;196(4286):180–182. doi: 10.1126/science.322279. [DOI] [PubMed] [Google Scholar]
  2. Boguski M. S., Elshourbagy N., Taylor J. M., Gordon J. I. Rat apolipoprotein A-IV contains 13 tandem repetitions of a 22-amino acid segment with amphipathic helical potential. Proc Natl Acad Sci U S A. 1984 Aug;81(16):5021–5025. doi: 10.1073/pnas.81.16.5021. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Breckenridge W. C., Roberts A., Kuksis A. Lipoprotein levels in genetically selected mice with increased susceptibility to atherosclerosis. Arteriosclerosis. 1985 May-Jun;5(3):256–264. doi: 10.1161/01.atv.5.3.256. [DOI] [PubMed] [Google Scholar]
  4. Breslow J. L. Human apolipoprotein molecular biology and genetic variation. Annu Rev Biochem. 1985;54:699–727. doi: 10.1146/annurev.bi.54.070185.003411. [DOI] [PubMed] [Google Scholar]
  5. Brown M. S., Kovanen P. T., Goldstein J. L. Regulation of plasma cholesterol by lipoprotein receptors. Science. 1981 May 8;212(4495):628–635. doi: 10.1126/science.6261329. [DOI] [PubMed] [Google Scholar]
  6. Buchberg A. M., Kinniburgh A. J. Induction of liver apolipoprotein A-IV mRNA in porphyric mice. Nucleic Acids Res. 1985 Mar 25;13(6):1953–1963. doi: 10.1093/nar/13.6.1953. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Carter A. D., Felber B. K., Walling M. J., Jubier M. F., Schmidt C. J., Hamer D. H. Duplicated heavy metal control sequences of the mouse metallothionein-I gene. Proc Natl Acad Sci U S A. 1984 Dec;81(23):7392–7396. doi: 10.1073/pnas.81.23.7392. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Castelli W. P., Doyle J. T., Gordon T., Hames C. G., Hjortland M. C., Hulley S. B., Kagan A., Zukel W. J. HDL cholesterol and other lipids in coronary heart disease. The cooperative lipoprotein phenotyping study. Circulation. 1977 May;55(5):767–772. doi: 10.1161/01.cir.55.5.767. [DOI] [PubMed] [Google Scholar]
  9. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  10. Chou P. Y., Fasman G. D. Empirical predictions of protein conformation. Annu Rev Biochem. 1978;47:251–276. doi: 10.1146/annurev.bi.47.070178.001343. [DOI] [PubMed] [Google Scholar]
  11. Church G. M., Gilbert W. Genomic sequencing. Proc Natl Acad Sci U S A. 1984 Apr;81(7):1991–1995. doi: 10.1073/pnas.81.7.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Elshourbagy N. A., Boguski M. S., Liao W. S., Jefferson L. S., Gordon J. I., Taylor J. M. Expression of rat apolipoprotein A-IV and A-I genes: mRNA induction during development and in response to glucocorticoids and insulin. Proc Natl Acad Sci U S A. 1985 Dec;82(23):8242–8246. doi: 10.1073/pnas.82.23.8242. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Feinberg A. P., Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. doi: 10.1016/0003-2697(83)90418-9. [DOI] [PubMed] [Google Scholar]
  14. Karathanasis S. K. Apolipoprotein multigene family: tandem organization of human apolipoprotein AI, CIII, and AIV genes. Proc Natl Acad Sci U S A. 1985 Oct;82(19):6374–6378. doi: 10.1073/pnas.82.19.6374. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Mahley R. W., Innerarity T. L., Rall S. C., Jr, Weisgraber K. H. Plasma lipoproteins: apolipoprotein structure and function. J Lipid Res. 1984 Dec 1;25(12):1277–1294. [PubMed] [Google Scholar]
  16. Maxam A. M., Gilbert W. Sequencing end-labeled DNA with base-specific chemical cleavages. Methods Enzymol. 1980;65(1):499–560. doi: 10.1016/s0076-6879(80)65059-9. [DOI] [PubMed] [Google Scholar]
  17. McMaster G. K., Carmichael G. G. Analysis of single- and double-stranded nucleic acids on polyacrylamide and agarose gels by using glyoxal and acridine orange. Proc Natl Acad Sci U S A. 1977 Nov;74(11):4835–4838. doi: 10.1073/pnas.74.11.4835. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Morrisett J. D., Kim H. S., Patsch J. R., Datta S. K., Trentin J. J. Genetic susceptibility and resistance to diet-induced atherosclerosis and hyperlipoproteinemia. Arteriosclerosis. 1982 Jul-Aug;2(4):312–324. doi: 10.1161/01.atv.2.4.312. [DOI] [PubMed] [Google Scholar]
  19. Paigen B., Morrow A., Brandon C., Mitchell D., Holmes P. Variation in susceptibility to atherosclerosis among inbred strains of mice. Atherosclerosis. 1985 Oct;57(1):65–73. doi: 10.1016/0021-9150(85)90138-8. [DOI] [PubMed] [Google Scholar]
  20. Rajavashisth T. B., Kaptein J. S., Reue K. L., Lusis A. J. Evolution of apolipoprotein E: mouse sequence and evidence for an 11-nucleotide ancestral unit. Proc Natl Acad Sci U S A. 1985 Dec;82(23):8085–8089. doi: 10.1073/pnas.82.23.8085. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Roberts A., Thompson J. S. Inbred mice and their hypbrids as an animal model for atherosclerosis research. Adv Exp Med Biol. 1976;67(00):313–327. doi: 10.1007/978-1-4614-4618-7_18. [DOI] [PubMed] [Google Scholar]
  22. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Segrest J. P., Jackson R. L., Morrisett J. D., Gotto A. M., Jr A molecular theory of lipid-protein interactions in the plasma lipoproteins. FEBS Lett. 1974 Jan 15;38(3):247–258. doi: 10.1016/0014-5793(74)80064-5. [DOI] [PubMed] [Google Scholar]
  24. Stuart G. W., Searle P. F., Chen H. Y., Brinster R. L., Palmiter R. D. A 12-base-pair DNA motif that is repeated several times in metallothionein gene promoters confers metal regulation to a heterologous gene. Proc Natl Acad Sci U S A. 1984 Dec;81(23):7318–7322. doi: 10.1073/pnas.81.23.7318. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Zinn K., DiMaio D., Maniatis T. Identification of two distinct regulatory regions adjacent to the human beta-interferon gene. Cell. 1983 Oct;34(3):865–879. doi: 10.1016/0092-8674(83)90544-5. [DOI] [PubMed] [Google Scholar]

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