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Gene Review

Apoe  -  apolipoprotein E

Mus musculus

Synonyms: AI255918, Apo-E, Apolipoprotein E
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Disease relevance of Apoe


Psychiatry related information on Apoe

  • Thus, Apoe seems to be important in the degradation and clearance of deposited Abeta species by astrocytes, a process that may be impaired in Alzheimer disease [5].
  • ApoE4 mice required more trials than apoE3 or Apoe-/- mice to reach criterion during passive avoidance training, but castration did not modulate passive avoidance learning or memory [6].
  • ApoE-deficient mouse has been employed as a serviceable model for studying the relation between apoE and the memory deficit induced by cholinergic impairment [7].
  • Repeated exposure to rats has persistent genotype-dependent effects on learning and locomotor activity of apolipoprotein E knockout and C57Bl/6 mice [8].
  • Daily NAPVSIPQ injections to newborn apolipoprotein E-deficient mice accelerated the acquisition of developmental reflexes and prevented short-term memory deficits [9].

High impact information on Apoe


Chemical compound and disease context of Apoe


Biological context of Apoe


Anatomical context of Apoe

  • Given the capacity of astrocytes to degrade Abeta, we investigated the potential role of Apoe in this astrocyte-mediated degradation [5].
  • Injection of activated wild-type, but not P-selectin-deficient, platelets increased monocyte arrest on the surface of atherosclerotic lesions and the size of atherosclerotic lesions in Apoe(-/-) mice [22].
  • To study isoform-specific effects of apolipoprotein E (apoE) in vivo, we generated mice with a human APOE*2 allele in place of the mouse Apoe gene via targeted gene replacement in embryonic stem cells [2].
  • Maximal plaque diameter (cross-section) was 37 +/- 74 micro m in SNX C57/BL6, 191 +/- 90 micro m in sham Apoe-/-, 323 +/- 66 micro m in UNX Apoe-/-, and 457 +/- 17 micro m in SNX Apoe-/-. The plaque morphology corresponded with that of early plaques characterized by foam cells and virtual absence of lymphocytes or smooth muscle cell infiltration [23].
  • In conclusion, even mild renal dysfunction, i.e., after uninephrectomy, causes a dramatic increase in plaque size and aggressive morphology (foam cell rich soft plaques) in the animal model of the Apoe-/- mouse [23].

Associations of Apoe with chemical compounds

  • Further reduction of apoE expression in hypoE/Apoe(-/-) heterozygous mice led to an increase in remnant lipoprotein-associated cholesterol levels, demonstrating that hypoE mice express close to the threshold level of Arg-61 apoE required for a normal lipoprotein profile [24].
  • To determine the chronic effects of reduced circulating androgen levels on susceptibility to the effects of apoE4 on cognitive function in males, we castrated and sham-castrated apoE4, apoE3, and Apoe-/- male mice and behaviorally compared them 3 months later [6].
  • In this study, we examined whether Apoe deletion affects the rewarding properties of ethanol in mice [25].
  • Male and female wild-type (WT; C57BL/6J) and apoE knockout (Apoe(-/-); C57BL/6J-Apoe(tm1Unc)) mice underwent an unbiased place conditioning procedure with ethanol (2 g/kg) or cocaine (5 mg/kg) [25].
  • Apoe(-/-) mice, which develop neurodegenerative alterations as they age, had an age-dependent increase in basal adrenal corticosterone content and abnormally increased plasma corticosterone levels after restraint stress, whereas their plasma and pituitary adrenocorticotropin levels were either unchanged or lower than those in controls [26].

Physical interactions of Apoe


Regulatory relationships of Apoe


Other interactions of Apoe


Analytical, diagnostic and therapeutic context of Apoe


  1. Lack of macrophage fatty-acid-binding protein aP2 protects mice deficient in apolipoprotein E against atherosclerosis. Makowski, L., Boord, J.B., Maeda, K., Babaev, V.R., Uysal, K.T., Morgan, M.A., Parker, R.A., Suttles, J., Fazio, S., Hotamisligil, G.S., Linton, M.F. Nat. Med. (2001) [Pubmed]
  2. Type III hyperlipoproteinemia and spontaneous atherosclerosis in mice resulting from gene replacement of mouse Apoe with human Apoe*2. Sullivan, P.M., Mezdour, H., Quarfordt, S.H., Maeda, N. J. Clin. Invest. (1998) [Pubmed]
  3. Hypertension and endothelial dysfunction in apolipoprotein E knockout mice. Yang, R., Powell-Braxton, L., Ogaoawara, A.K., Dybdal, N., Bunting, S., Ohneda, O., Jin, H. Arterioscler. Thromb. Vasc. Biol. (1999) [Pubmed]
  4. The transport of triglycerides through the secretory pathway of hepatocytes is impaired in apolipoprotein E deficient mice. Mensenkamp, A.R., Van Luyn, M.J., Havinga, R., Teusink, B., Waterman, I.J., Mann, C.J., Elzinga, B.M., Verkade, H.J., Zammit, V.A., Havekes, L.M., Shoulders, C.C., Kuipers, F. J. Hepatol. (2004) [Pubmed]
  5. Apolipoprotein E promotes astrocyte colocalization and degradation of deposited amyloid-beta peptides. Koistinaho, M., Lin, S., Wu, X., Esterman, M., Koger, D., Hanson, J., Higgs, R., Liu, F., Malkani, S., Bales, K.R., Paul, S.M. Nat. Med. (2004) [Pubmed]
  6. Role of circulating androgen levels in effects of apoE4 on cognitive function. Pfankuch, T., Rizk, A., Olsen, R., Poage, C., Raber, J. Brain Res. (2005) [Pubmed]
  7. Cerebral protein kinase C and its mRNA level in apolipoprotein E-deficient mice. Hung, M.C., Hayase, K., Yoshida, R., Sato, M., Imaizumi, K. Life Sci. (2001) [Pubmed]
  8. Repeated exposure to rats has persistent genotype-dependent effects on learning and locomotor activity of apolipoprotein E knockout and C57Bl/6 mice. Grootendorst, J., de Kloet, E.R., Vossen, C., Dalm, S., Oitzl, M.S. Behav. Brain Res. (2001) [Pubmed]
  9. Complete sequence of a novel protein containing a femtomolar-activity-dependent neuroprotective peptide. Bassan, M., Zamostiano, R., Davidson, A., Pinhasov, A., Giladi, E., Perl, O., Bassan, H., Blat, C., Gibney, G., Glazner, G., Brenneman, D.E., Gozes, I. J. Neurochem. (1999) [Pubmed]
  10. LDL receptor-related protein, a multifunctional ApoE receptor, binds secreted beta-amyloid precursor protein and mediates its degradation. Kounnas, M.Z., Moir, R.D., Rebeck, G.W., Bush, A.I., Argraves, W.S., Tanzi, R.E., Hyman, B.T., Strickland, D.K. Cell (1995) [Pubmed]
  11. Severe hypercholesterolemia and atherosclerosis in apolipoprotein E-deficient mice created by homologous recombination in ES cells. Plump, A.S., Smith, J.D., Hayek, T., Aalto-Setälä, K., Walsh, A., Verstuyft, J.G., Rubin, E.M., Breslow, J.L. Cell (1992) [Pubmed]
  12. The 5-lipoxygenase pathway promotes pathogenesis of hyperlipidemia-dependent aortic aneurysm. Zhao, L., Moos, M.P., Gräbner, R., Pédrono, F., Fan, J., Kaiser, B., John, N., Schmidt, S., Spanbroek, R., Lötzer, K., Huang, L., Cui, J., Rader, D.J., Evans, J.F., Habenicht, A.J., Funk, C.D. Nat. Med. (2004) [Pubmed]
  13. Diet-induced hypercholesterolemia and atherosclerosis in heterozygous apolipoprotein E-deficient mice. van Ree, J.H., van den Broek, W.J., Dahlmans, V.E., Groot, P.H., Vidgeon-Hart, M., Frants, R.R., Wieringa, B., Havekes, L.M., Hofker, M.H. Atherosclerosis (1994) [Pubmed]
  14. Apolipoprotein E knock-out mice are highly susceptible to endotoxemia and Klebsiella pneumoniae infection. de Bont, N., Netea, M.G., Demacker, P.N., Verschueren, I., Kullberg, B.J., van Dijk, K.W., van der Meer, J.W., Stalenhoef, A.F. J. Lipid Res. (1999) [Pubmed]
  15. Mice deficient in apolipoprotein E but not LDL receptors are resistant to accelerated atherosclerosis associated with obesity. Schreyer, S.A., Lystig, T.C., Vick, C.M., LeBoeuf, R.C. Atherosclerosis (2003) [Pubmed]
  16. Is there a role for the macrophage 5-lipoxygenase pathway in aortic aneurysm development in apolipoprotein e-deficient mice? Funk, C.D., Cao, R.Y., Zhao, L., Habenicht, A.J. Ann. N. Y. Acad. Sci. (2006) [Pubmed]
  17. Inhibition by a coantioxidant of aortic lipoprotein lipid peroxidation and atherosclerosis in apolipoprotein E and low density lipoprotein receptor gene double knockout mice. Witting, P.K., Pettersson, K., Ostlund-Lindqvist, A.M., Westerlund, C., Eriksson, A.W., Stocker, R. FASEB J. (1999) [Pubmed]
  18. Genetic modification of the phenotypes produced by amyloid precursor protein overexpression in transgenic mice. Carlson, G.A., Borchelt, D.R., Dake, A., Turner, S., Danielson, V., Coffin, J.D., Eckman, C., Meiners, J., Nilsen, S.P., Younkin, S.G., Hsiao, K.K. Hum. Mol. Genet. (1997) [Pubmed]
  19. Inactivation of Apoe and Apoc1 by two consecutive rounds of gene targeting: effects on mRNA expression levels of gene cluster members. van Ree, J.H., van den Broek, W.J., van der Zee, A., Dahlmans, V.E., Wieringa, B., Frants, R.R., Havekes, L.M., Hofker, M.H. Hum. Mol. Genet. (1995) [Pubmed]
  20. Genetic factors controlling structure and expression of apolipoproteins B and E in mice. Lusis, A.J., Taylor, B.A., Quon, D., Zollman, S., LeBoeuf, R.C. J. Biol. Chem. (1987) [Pubmed]
  21. ApoB-48 and apoB-100 differentially influence the expression of type-III hyperlipoproteinemia in APOE*2 mice. Hinsdale, M.E., Sullivan, P.M., Mezdour, H., Maeda, N. J. Lipid Res. (2002) [Pubmed]
  22. Circulating activated platelets exacerbate atherosclerosis in mice deficient in apolipoprotein E. Huo, Y., Schober, A., Forlow, S.B., Smith, D.F., Hyman, M.C., Jung, S., Littman, D.R., Weber, C., Ley, K. Nat. Med. (2003) [Pubmed]
  23. The apolipoprotein e knockout mouse: a model documenting accelerated atherogenesis in uremia. Buzello, M., Törnig, J., Faulhaber, J., Ehmke, H., Ritz, E., Amann, K. J. Am. Soc. Nephrol. (2003) [Pubmed]
  24. Hypomorphic apolipoprotein E mice: a new model of conditional gene repair to examine apolipoprotein E-mediated metabolism. Raffai, R.L., Weisgraber, K.H. J. Biol. Chem. (2002) [Pubmed]
  25. Enhanced ethanol-, but not cocaine-induced, conditioned place preference in Apoe(-/-) mice. Bechtholt, A.J., Smith, R., Raber, J., Cunningham, C.L. Pharmacol. Biochem. Behav. (2004) [Pubmed]
  26. Hypothalamic-pituitary-adrenal dysfunction in Apoe(-/-) mice: possible role in behavioral and metabolic alterations. Raber, J., Akana, S.F., Bhatnagar, S., Dallman, M.F., Wong, D., Mucke, L. J. Neurosci. (2000) [Pubmed]
  27. Structure of a monoclonal 2E8 Fab antibody fragment specific for the low-density lipoprotein-receptor binding region of apolipoprotein E refined at 1.9 A. Trakhanov, S., Parkin, S., Raffaï, R., Milne, R., Newhouse, Y.M., Weisgraber, K.H., Rupp, B. Acta Crystallogr. D Biol. Crystallogr. (1999) [Pubmed]
  28. Apolipoprotein E and Reelin ligands modulate tau phosphorylation through an apolipoprotein E receptor/disabled-1/glycogen synthase kinase-3beta cascade. Ohkubo, N., Lee, Y.D., Morishima, A., Terashima, T., Kikkawa, S., Tohyama, M., Sakanaka, M., Tanaka, J., Maeda, N., Vitek, M.P., Mitsuda, N. FASEB J. (2003) [Pubmed]
  29. Differential effects of interleukin-1 receptor antagonist and tumor necrosis factor binding protein on fatty-streak formation in apolipoprotein E-deficient mice. Elhage, R., Maret, A., Pieraggi, M.T., Thiers, J.C., Arnal, J.F., Bayard, F. Circulation (1998) [Pubmed]
  30. A 13 kDa carboxy-terminal fragment of ApoE stabilizes Abeta hexamers. Wellnitz, S., Friedlein, A., Bonanni, C., Anquez, V., Goepfert, F., Loetscher, H., Adessi, C., Czech, C. J. Neurochem. (2005) [Pubmed]
  31. Phosphorylation of tau in apolipoprotein E-deficient mice. Genis, I., Gordon, I., Sehayek, E., Michaelson, D.M. Neurosci. Lett. (1995) [Pubmed]
  32. Hypercholesterolemia exacerbates virus-induced immunopathologic liver disease via suppression of antiviral cytotoxic T cell responses. Ludewig, B., Jäggi, M., Dumrese, T., Brduscha-Riem, K., Odermatt, B., Hengartner, H., Zinkernagel, R.M. J. Immunol. (2001) [Pubmed]
  33. Cyclooxygenase-2 promotes early atherosclerotic lesion formation in ApoE-deficient and C57BL/6 mice. Burleigh, M.E., Babaev, V.R., Yancey, P.G., Major, A.S., McCaleb, J.L., Oates, J.A., Morrow, J.D., Fazio, S., Linton, M.F. J. Mol. Cell. Cardiol. (2005) [Pubmed]
  34. Macrophage low-density lipoprotein receptor-related protein deficiency enhances atherosclerosis in ApoE/LDLR double knockout mice. Hu, L., Boesten, L.S., May, P., Herz, J., Bovenschen, N., Huisman, M.V., Berb??e, J.F., Havekes, L.M., van Vlijmen, B.J., Tamsma, J.T. Arterioscler. Thromb. Vasc. Biol. (2006) [Pubmed]
  35. Adiponectin reduces atherosclerosis in apolipoprotein E-deficient mice. Okamoto, Y., Kihara, S., Ouchi, N., Nishida, M., Arita, Y., Kumada, M., Ohashi, K., Sakai, N., Shimomura, I., Kobayashi, H., Terasaka, N., Inaba, T., Funahashi, T., Matsuzawa, Y. Circulation (2002) [Pubmed]
  36. Adeno-associated virus vector-mediated interleukin-10 gene transfer inhibits atherosclerosis in apolipoprotein E-deficient mice. Yoshioka, T., Okada, T., Maeda, Y., Ikeda, U., Shimpo, M., Nomoto, T., Takeuchi, K., Nonaka-Sarukawa, M., Ito, T., Takahashi, M., Matsushita, T., Mizukami, H., Hanazono, Y., Kume, A., Ookawara, S., Kawano, M., Ishibashi, S., Shimada, K., Ozawa, K. Gene Ther. (2004) [Pubmed]
  37. P-Selectin or intercellular adhesion molecule (ICAM)-1 deficiency substantially protects against atherosclerosis in apolipoprotein E-deficient mice. Collins, R.G., Velji, R., Guevara, N.V., Hicks, M.J., Chan, L., Beaudet, A.L. J. Exp. Med. (2000) [Pubmed]
  38. Cholesterol lowering in low density lipoprotein receptor knockout mice overexpressing apolipoprotein E. Osuga, J., Yonemoto, M., Yamada, N., Shimano, H., Yagyu, H., Ohashi, K., Harada, K., Kamei, T., Yazaki, Y., Ishibashi, S. J. Clin. Invest. (1998) [Pubmed]
  39. Conditional disruption of the peroxisome proliferator-activated receptor gamma gene in mice results in lowered expression of ABCA1, ABCG1, and apoE in macrophages and reduced cholesterol efflux. Akiyama, T.E., Sakai, S., Lambert, G., Nicol, C.J., Matsusue, K., Pimprale, S., Lee, Y.H., Ricote, M., Glass, C.K., Brewer, H.B., Gonzalez, F.J. Mol. Cell. Biol. (2002) [Pubmed]
  40. Deletion of the alternatively spliced fibronectin EIIIA domain in mice reduces atherosclerosis. Tan, M.H., Sun, Z., Opitz, S.L., Schmidt, T.E., Peters, J.H., George, E.L. Blood (2004) [Pubmed]
  41. Scrapie in mice deficient in apolipoprotein E or glial fibrillary acidic protein. Tatzelt, J., Maeda, N., Pekny, M., Yang, S.L., Betsholtz, C., Eliasson, C., Cayetano, J., Camerino, A.P., DeArmond, S.J., Prusiner, S.B. Neurology (1996) [Pubmed]
  42. Loss of receptor-mediated lipid uptake via scavenger receptor A or CD36 pathways does not ameliorate atherosclerosis in hyperlipidemic mice. Moore, K.J., Kunjathoor, V.V., Koehn, S.L., Manning, J.J., Tseng, A.A., Silver, J.M., McKee, M., Freeman, M.W. J. Clin. Invest. (2005) [Pubmed]
  43. Spontaneously hyperlipidemic (SHL) mice: Japanese wild mice with apolipoprotein E deficiency. Matsushima, Y., Hayashi, S., Tachibana, M. Mamm. Genome (1999) [Pubmed]
  44. The evolution of A beta peptide burden in the APP23 transgenic mice: implications for A beta deposition in Alzheimer disease. Kuo, Y.M., Beach, T.G., Sue, L.I., Scott, S., Layne, K.J., Kokjohn, T.A., Kalback, W.M., Luehrs, D.C., Vishnivetskaya, T.A., Abramowski, D., Sturchler-Pierrat, C., Staufenbiel, M., Weller, R.O., Roher, A.E. Mol. Med. (2001) [Pubmed]
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