Overproduction of cholesterol and fatty acids causes massive liver enlargement in transgenic mice expressing truncated SREBP-1a

Journal of Clinical Investigation

Volumn 98, Issue 7, 1996, Pages 1575-1584

  Shimano, Hitoshi ^a   Horton, Jay D ^a   Hammer, Robert E ^b   Shimomura, Iichiro ^a   Brown, Michael S ^a   Goldstein, Joseph L ^a  

^a UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

^b HOWARD HUGHES MEDICAL INSTITUTE   (United States)

Author keywords

cholesterol; fatty acids; LDL receptors; SREBP; transgenic mice

Indexed keywords

ACETYL COENZYME A SYNTHETASE; ACYL COENZYME A DESATURASE; CHOLESTEROL; DNA BINDING PROTEIN; FATTY ACID; FATTY ACID SYNTHASE; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE; SQUALENE SYNTHASE;

ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CATABOLITE REPRESSION; CHOLESTEROL SYNTHESIS; CONTROLLED STUDY; FATTY ACID SYNTHESIS; FEEDBACK SYSTEM; HEPATOMEGALY; MOUSE; NONHUMAN; PRIORITY JOURNAL; TRANSGENIC MOUSE;

EID: 0029797604     PISSN: 00219738     EISSN: None     Source Type: Journal    
DOI: 10.1172/JCI118951     Document Type: Article

References (61)

1. Gould, R.G. 1951. Lipid metabolism and atherosclerosis. Am. J. Med. 11: 209-227.
2. Gould, R.G., B. Taylor, J.S. Hagerman, I. Warner, and D.J. Campbell. 1953. Cholesterol metabolism. 1. Effect of dietary cholesterol on the synthesis of cholesterol in dog tissue in vitro. J. Biol. Chem. 201:519-523.
3. Bucher, N.L.R., P. Overath, and F. Lynen. 1960. β-Hydroxy-β-methylglutaryl coenzyme A reductase, cleavage and condensing enzymes in relation to cholesterol formation in rat liver. Biochim. Biophys. Acta. 40:491-501.
4. Siperstein, M.D., and V.M. Fagan. 1966. Feedback control of mevalonate synthesis by dietary cholesterol. J. Biol. Chem. 241:602-609.
5. Clinkenbeard, K.D., T. Sugiyama, W.D. Reed, and M.D. Lane. 1975. Cytoplasmic 3-hydroxy-3-methylglutaryl coenzyme A synthase from liver: Purification, properties, and role in cholesterol synthesis. J. Biol. Chem. 250:3124-3135.
6. Clarke, C.F., R.D. Tanaka, K. Svenson, M. Wamsley, A.M. Fogelman, and P.A. Edwards. 1987. Molecular cloning and sequence of a cholesterol-repressible enzyme related to prenyltransferase in the isoprene biosynthetic pathway. Mol. Cell. Biol. 7:3138-3146.
7. Gould, R.G., and E.A. Swyryd. 1966. Sites of control of hepatic cholesterol byosynthesis. J. Lipid Res. 7:698-707.
8. Shechter, I., E. Klinger, M.L. Rucker, R.G. Engstrom, J.A. Spirito, M.A. Islam, B.R. Boettcher, and D.B. Weinstein. 1992. Sulubilization, purification, and characterization of a truncated form of ral hepatic squalene synthetase. J. Biol. Chem. 267:8628-8635.
9. Horton, J.D., J.A. Cuthbert, and D.K. Spady. 1995. Regulation of hepatic 7α-hydroxylase expression and response to dietary cholesterol in the rat and hamster. J. Biol. Chem. 270:5381-5387.
10. Sorci-Thomas, M., M.D. Wilson, F.L. Johnson, D.L. Williams, and L.L. Rudel. 1989. Studies on the expression of genes encoding apolipoproteins B100 and B48 and the low density lipoprotein receptor in nonhuman primates: comparison of dietary fat and cholesterol. J. Biol. Chem. 264:9039-91145.
11. Wang, X., R. Sato, M.S. Brown, X. Hua, and J.L. Goldstein. 1994. SREBP-1, a membrane-bound transcription factor released by sterol-regulated proteolysis. Cell. 77:53-62.
12. Yokoyama, C., X. Wang, M.R. Briggs, A. Admon, J. Wu, X. Hua, J.L. Goldstein, and M.S. Brown. 1993. SREBP-1, a basic helix-loop-helix leucine zipper protein that controls transcription of the LDL receptor gene. Cell. 75: 187-197.
13. Hua, X., C. Yokoyama, J. Wu, M.R. Briggs, M.S. Brown, J.L. Goldstein, and X. Wang. 1993. SREBP-2, a second basic-helix-loop-helix-leucine zipper protein that stimulates transcription by binding to a sterol regulatory element. Proc. Natl. Acad. Sci. USA. 90:11603-11607.
14. Hua, X., J. Sakai, Y.K. Ho, J.L. Goldstein, and M.S. Brown. 1995. Hairpin orientation of sterol regulatory element binding protein-2 in cell membranes as determined by protease protection. J. Biol. Chem. 270:29422-29427.
15. Hua, X., J. Sakai, M.S. Brown, and J.L. Goldstein. 1996. Regulated cleavage of sterol regulatory element binding proteins (SREBPs) requires sequences on both sides of the endoplasmic reticulum membrane. J. Biol. Chem. 271:10379-10384.
16. Sakai, J., E.A. Duncan, R.B. Rawson, X. Hua, M.S. Brown, and J.L. Goldstein. 1996. Sterol-regulated release of SREBP-2 from cell membranes requires two sequential cleavages, one within a transmembrane segment. Cell. 85: 1037-1046.
17. Sato, R., J. Yang, X. Wang, M.J. Evans, Y. K. Ho, J.L. Goldstein, and M.S. Brown. 1994. Assignment of the membrane attachment. DNA binding, and transcriptional activation domains of sterol regulatory element binding protein-1 (SREBP-1). J. Biol. Chem. 269:17267-17273.
18. Yang, J., M.S. Brown Y.K. Ho, and J.L. Goldstein. 1995. Three different rearrangements in a single intron truncate SREBP-2 and produce sterol-resistant phenotype in three cell lines. J. Biol. Chem 270:12152-12161.
19. Yang, J., R. Sato, J.L. Goldstein, and M.S. Brown. 1994. Sterol-resistant transcription in CHO cells caused by gene rearrangement that truncates SREBP-2. Genes & Dev. 8:1910-1919.
20. Wang, X., M.R. Briggs, X. Hua, C. Yokoyama, J.L. Goldstein, and M.S. Brown. 1993. Nuclear protein that binds sterol regulatory element of LDL receptor promoter. II. Purification and characterization. J. Biol. Chem. 268:14497-14504.
21. Ericsson, J., S.M. Jackson, B.C. Lee, and P.A. Edwards. 1996. Sterol regulatory element binding protein binds to a cis element in the promoter of the farnesyl diphosphate synthase gene. Proc. Natl. Acad. Sci. USA. 93:945-950.
22. Guan, G., G. Jiang, R.L. Koch, and I. Shechter. 1995. Molecular cloning and functional analysis of the promoter of the human squalene synthase gene. J. Biol. Chem. 270:21958-21965.
23. Vallett, S.M., H.B. Sanchez, J.M. Rosenfeld, and T.F. Osborne. 1996. A direct role for sterol regulatory element binding protein in activation of 3-hydroxy-3-methylglutaryl coenzyme a reductase gene. J. Biol. Chem. 271:12247-12253.
24. Lopez, J.M., M.K. Bennett, H.B. Sanchez, J.M. Rosenfeld, and T.F. Osborne. 1996. Sterol regulation of acetyl CoA carboxylase: A mechanism for coordinate control of cellular lipid. Proc. Natl. Acad. Sci. USA. 93:1049-1053.
25. Bennett, M.K., J.M. Lopez, H.B. Sanchez, and T.F. Osborne. 1995. Sterol regulation of fatty acid synthase promoter: Coordinate feedback regulation of two major lipid pathways. J. Biol. Chem. 270:25578-25583.
26. Hua, X., J. Wu, J.L. Goldstein, M.S. Brown, and H.H. Hobbs. 1995. Structure of human gene encoding sterol regulatory element binding protein-1 (SREBF1) and localization of SREBF1 and SREBF2 to chromosomes 17p11.2 and 22q13. Genomics. 25:667-673.
27. Sheng, Z., H. Otani, M.S. Brown, and J.L. Goldstein. 1995. Independent regulation of sterol regulatory element binding proteins 1 and 2 in hamster liver. Proc. Natl. Acad. Sci. USA. 92:935-938.
28. Sambrook, J., E.F. Fritsch, and T. Maniatis. 1989. Molecular Cloning: A Laboratory Manual. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY.
29. Yokode, M., R.E. Hammer, S. Ishibashi, M.S. Brown, and J.L. Goldstein. 1990. Diet-induced hypercholesterolemia in mice: Prevention by overexpression of LDL receptors. Science (Wash. DC). 250:1273-1275.
30. Bucolo, G., and H. David. 1973. Quantitative determination of serum triglycerides by the use of enzymes. Clin. Chem. 19:476-482.
31. Short, M.K., D.E. Clouthier, I.M. Schaefer, R.E. Hammer, M.A. Magnuson, and F.G. Beale. 1992. Tissue-specific, developmental, hormonal, and dietary regulation of rat phosphoenolpyruvate carboxykinase-human growth hormone fusion genes in transgenic mice. Mol. Cell. Biol. 12:1007-1020.
32. Hofmann, S.L., D.W. Russell, M.S. Brown, J.L. Goldstein, and R.E. Hammer. 1988. Overexpression of low density lipoprotein (LDL) receptor eliminates LDL from plasma in transgenic mice. Science (Wash. DC). 239:1277-1281.
33. Chen, C.W., and C.A. Thomas, Jr. 1980. Recovery of DNA segments from agarose gels. Anal. Biochem. 101:339-341.
34. Ishibashi, S., M.S. Brown, J.L. Goldstein, R.D. Gerard, R.E. Hammer, and J. Herz. 1993. Hypercholesterolemia in LDL receptor knockout mice and its reversal by adenovirus-mediated gene delivery. J. Clin. Invest. 92:883-893.
35. Ishibashi, S., M. Schwarz, P. Frykman, D.W. Russell, and J. Herz. 1996. Disruption of cholesterol 7α-hydroxylase gene in mice. I. Postnatal lethality reversed by bile acid and vitamin supplementation. J. Biol. Chem 271:18017-18023.
36. cis farnesyltransferase, the counterpart of yeast DPR1/RAM1. Cell. 66: 327-334.
37. Kirchgessner, T.G., K.L. Svenson, A.J. Lusis, and M.C. Schotz. 1987. The sequence of cDNA encoding lipoprotein lipase: a member of a lipase gene family. J. Biol. Chem. 262:8463-8466.
38. Tokunaga, K., H. Taniguchi, K. Yoda, M. Shimizu, and S. Sakiyama. 1986. Nucleotide sequence of a full-length cDNA for mouse cytoskeletal β-actin mRNA. Nucleic Acids Res. 14:2829.
39. Beisiegel, U., W.J. Schneider, J.L. Goldstein, R.G.W. Anderson, and M.S. Brown. 1981. Monoclonal antibodies to the low density lipoprotein receptor as probes for study of receptor-mediated endocytosis and the genetics of familial hypercholesterolemia. J. Biol. Chem. 256:11923-11931.
40. Osono, Y., L.A. Woollett, J. Herz, and J.M. Dietschy. 1995. Role of the low density lipoprotein receptor in the flux of cholesterol through the plasma and across the tissues of the mouse. J. Clin. Invest. 95:1124-1132.
41. Dietschy, J.M., and D.K. Spady. 1984. Measurement of rates of cholesterol synthesis using tritiated water. J. Lipid Res 25:1469-1476.
42. Lowenstein, J.M., H. Brunengraber, and M. Wadke. 1975. Measurement of rates of lipogenesis with deuterated and tritiated water. Methods Enzymol. 35B:279-287.
43. Spady, D.K., and J.M. Dietschy. 1983. Sterol synthesis in vivo in 18 tissues of the squirrel monkey, guinea pig, rabbit, hamster, and rat. J. Lipid Res. 24:303-315.
44. 129 mutant enzymes. Arch. Biochem. Biophys. 312:1-13.
45. Gil, G., J.L. Goldstein, C.A. Slaughter, and M.S. Brown. 1986. Cytoplasmic 3-hydroxy-3-methylglutaryl coenzyme A synthase from the hamster. I. Isolation and sequencing of a full-length cDNA. J. Biol. Chem. 261:3710-3716.
46. Chin, D.J., G. Gil, D.W. Russell, L. Liscum, K.L. Luskey, S.K. Basu, H. Okayama, P. Berg, J.L. Goldstein, and M.S. Brown. 1984. Nucleotide sequence of 3-hydroxy-3-methylglutaryl CoA reductase, a glycoprotein of the endoplasmic reticulum. Nature (Lond.). 308:613-617.
47. Amy, C.M., A. Witkowski, J. Naggert, B. Williams, Z. Randhawa, and S. Smith. 1989. Molecular cloning and sequencing of cDNAs encoding the entire rat fatty acid synthase. Proc. Natl. Acad. Sci. USA. 86:3114-3118.
48. Yuan, Z., W. Liu, and G.G. Hammes. 1988. Molecular cloning and sequencing of DNA complementary to chicken liver fatty acid synthase mRNA. Proc. Natl. Acad. Sci. USA. 85:6328-6331.
49. Ha, J., S. Daniel, I.-S. Kong, C.-K. Park, H.-J. Tae, and K.-H. Kim. 1994. Cloning of human acetyl-CoA carboxylase cDNA. Eur. J. Biochem. 219:297-306.
50. Lopez-Casillas, F., D.-H. Bai, X. Luo, I.-S. Kong, M.A. Hermodson, and K.-H. Kim. 1988. Structure of the coding sequence and primary amino acid sequence of acetyl-coenzyme A carboxylase. Proc. Natl. Acad. Sci. USA. 85:5784-5788.
51. Inoue, T., T. Osumi, and S. Hata. 1995. Molecular cloning and functional expression of a cDNA for mouse squalene synthase. Biochem. Biophy. Acta. 1260:49-54.
52. Ntambi, J.M., S.A. Buhrow, K.H. Kaestner, R.J. Christy, E. Sibley, T.J. Kelly, Jr., and M.D. Lane. 1988. Differentiation-induced gene expression in 3T3-L1 preadipocytes. J. Biol. Chem. 263:17291-17300.
53. Poncin, J.E., J.A. Martial, and J.E. Gielen. 1984. Cloning and structure analysis of the rat apolipoprotein A-I cDNA. Eur. J. Biochem. 140:493-498.
54. Shoulders, C.C., A.R. Kornblihtt, B.S. Munro, and F.E. Baralle. 1983. Gene structure of human apolipoprotein A1. Nucleic Acids Res. 11:2827-2837.
55. Matsumoto, A., H. Ahuratani, Y., Shibasaki, T. Kodama, F. Takaku, and H. Itakura. 1987. Cloning and regulation of rat apolipoprotein B mRNA. Biochem. Biophys. Res. Comm. 142:92-99.
56. Yang, C.-Y., S.-H. Chen, S.H. Gianturco, W.A. Bradley, J.T. Sparrow, M. Tanimura, W.-H. Li, D. A. Sparrow, H. DeLoof, M. Rosseneu, F.-S. Lee, Z.-W. Gu, A. M. Gotto, Jr., and L. Chan. 1986. Sequence, structure, receptor-binding domains and internal repeats of human apolipoprotein B-100. Nature (Lond.). 323:738-742.
57. Rajavashisth, T.B., J.S. Kaptein, K.L. Reue, and A.J. Lusis. 1985. Evolution of apolipoprotein E: Mouse sequence and evidence for an 11-nucleotide ancestral unit. Proc. Natl. Acad. Sci. USA. 82:8085-8089.
58. Ginsberg, H.N. 1995. Synthesis and secretion of apolipoprotein B from cultured liver cells. Curr. Opin. Lipidol. 6:275-280.
59. Reynolds, G.A., J.L. Goldstein, and M.S. Brown. 1985. Multiple mRNAs for 3-hydroxy-3-methylglutaryl coenzyme A reductase determined by multiple transcription initiation sites and intron splicing sites in the 5′ untranslated region. J. Biol. Chem. 260:10369-10377.
60. Siperstein, M.D., and M.J. Guest. 1960. Studies on the site of the feedback control of cholesterol synthesis. J. Clin. Invest. 39:642-652.
61. Kim, J.B., and B.M. Spiegelman. 1996. ADD1/SREBP1 promotes adipocyte differentiation and gene expression linked to fatty acid metabolism. Genes Dev. 10:1096-1107.