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Mttp  -  microsomal triglyceride transfer protein

Mus musculus

Synonyms: 1810043K16Rik, MTP, Microsomal triglyceride transfer protein large subunit, Mtp
 
 
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Disease relevance of Mttp

  • Conditional deletion of the Mttp gene in hepatocytes is associated with a redistribution of CD1d expression, and Mttp-deleted mice are resistant to immunopathologies associated with invariant NKT cell-mediated hepatitis and colitis [1].
  • In marked contrast to the MTP-deficient model of fatty liver, electron microscopy of lipid-stained liver sections of Apoe(-/-) mice revealed an accumulation of lipid in numerous small, putative ER-derived vesicles and in the cytosol [2].
  • Mutations in MTP are a major cause of abetalipoproteinemia [3].
  • FAO rat hepatoma cells express L-FABP and MTP and demonstrate the ability to assemble and secrete VLDL [4].
  • We constructed a recombinant adenovirus expressing MTP (AdhMTP) and used it to assess the effects of hepatic overexpression of MTP in mice [5].
 

High impact information on Mttp

 

Biological context of Mttp

  • All homozygous embryos (Mttp-/-) died during embryonic development [7].
  • These observations prompted us to examine the phenotype following intestine-specific Mttp deletion because murine, like human enterocytes, secrete virtually exclusively apoB48 [8].
  • We generated mice with conditional Mttp deletion in villus enterocytes (Mttp-IKO), using a tamoxifen-inducible, intestine-specific Cre transgene [8].
  • Compensatory increase in hepatic lipogenesis in mice with conditional intestine-specific Mttp deficiency [8].
  • The DNA-deduced amino acid sequence indicates that mouse MTP contains 894 amino acids; the mouse protein shows 93, 86, and 83% sequence identity to the hamster, human, and bovine sequences, respectively [3].
 

Anatomical context of Mttp

 

Associations of Mttp with chemical compounds

 

Physical interactions of Mttp

 

Co-localisations of Mttp

  • Morphometric analyses indicated that approximately 17% of the MTP signal colocalized with the TGN38, while 33% of the trans-Golgi marker colocalized with the MTP [15].
 

Regulatory relationships of Mttp

  • In conclusion, PPARalpha activation stimulates hepatic MTP expression via increased transcription of the Mtp gene [11].
 

Other interactions of Mttp

 

Analytical, diagnostic and therapeutic context of Mttp

  • After Cre induction, hepatic Mttp expression was virtually eliminated (as judged by quantitative real-time PCR), hepatic lipoprotein secretion was abolished (as judged by electron microscopy), and LDLs were virtually eliminated from the plasma [18].
  • To characterize the ontogeny of MTP expression during embryonic mouse development, we have used in situ hybridization to characterize the pattern of expression [19].
  • Concerning the addition of core neutral lipids in the later stages of lipoprotein assembly, cell culture studies show that MTP lipid transfer activity is not required for this to occur for apolipoprotein B-100 containing lipoproteins [20].
  • We show MTP RNA and protein in antigen-presenting cells (APCs) by reverse transcription-polymerase chain reaction and by immunoblotting of mouse liver mononuclear cells and mouse and human B cell lines [21].
  • NKT cells fail to develop in fetal thymic organ culture (FTOC) treated with MTP antagonists [6].

References

  1. CD1d function is regulated by microsomal triglyceride transfer protein. Brozovic, S., Nagaishi, T., Yoshida, M., Betz, S., Salas, A., Chen, D., Kaser, A., Glickman, J., Kuo, T., Little, A., Morrison, J., Corazza, N., Kim, J.Y., Colgan, S.P., Young, S.G., Exley, M., Blumberg, R.S. Nat. Med. (2004) [Pubmed]
  2. 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]
  3. Mouse microsomal triglyceride transfer protein large subunit: cDNA cloning, tissue-specific expression and chromosomal localization. Nakamuta, M., Chang, B.H., Hoogeveen, R., Li, W.H., Chan, L. Genomics (1996) [Pubmed]
  4. Coordinate Transcriptional Repression of Liver Fatty Acid-binding Protein and Microsomal Triglyceride Transfer Protein Blocks Hepatic Very Low Density Lipoprotein Secretion without Hepatosteatosis. Spann, N.J., Kang, S., Li, A.C., Chen, A.Z., Newberry, E.P., Davidson, N.O., Hui, S.T., Davis, R.A. J. Biol. Chem. (2006) [Pubmed]
  5. Hepatic overexpression of microsomal triglyceride transfer protein (MTP) results in increased in vivo secretion of VLDL triglycerides and apolipoprotein B. Tietge, U.J., Bakillah, A., Maugeais, C., Tsukamoto, K., Hussain, M., Rader, D.J. J. Lipid Res. (1999) [Pubmed]
  6. MTP regulated by an alternate promoter is essential for NKT cell development. Dougan, S.K., Rava, P., Hussain, M.M., Blumberg, R.S. J. Exp. Med. (2007) [Pubmed]
  7. Knockout of the abetalipoproteinemia gene in mice: reduced lipoprotein secretion in heterozygotes and embryonic lethality in homozygotes. Raabe, M., Flynn, L.M., Zlot, C.H., Wong, J.S., Véniant, M.M., Hamilton, R.L., Young, S.G. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  8. Compensatory increase in hepatic lipogenesis in mice with conditional intestine-specific Mttp deficiency. Xie, Y., Newberry, E.P., Young, S.G., Robine, S., Hamilton, R.L., Wong, J.S., Luo, J., Kennedy, S., Davidson, N.O. J. Biol. Chem. (2006) [Pubmed]
  9. A deficiency of microsomal triglyceride transfer protein reduces apolipoprotein B secretion. Leung, G.K., Véniant, M.M., Kim, S.K., Zlot, C.H., Raabe, M., Björkegren, J., Neese, R.A., Hellerstein, M.K., Young, S.G. J. Biol. Chem. (2000) [Pubmed]
  10. Blocking microsomal triglyceride transfer protein interferes with apoB secretion without causing retention or stress in the ER. Liao, W., Hui, T.Y., Young, S.G., Davis, R.A. J. Lipid Res. (2003) [Pubmed]
  11. Activation of peroxisome proliferator-activated receptor alpha increases the expression and activity of microsomal triglyceride transfer protein in the liver. Améen, C., Edvardsson, U., Ljungberg, A., Asp, L., Akerblad, P., Tuneld, A., Olofsson, S.O., Lindén, D., Oscarsson, J. J. Biol. Chem. (2005) [Pubmed]
  12. Inhibition of microsomal triglyceride transfer protein: another mechanism for drug-induced steatosis in mice. Lettéron, P., Sutton, A., Mansouri, A., Fromenty, B., Pessayre, D. Hepatology (2003) [Pubmed]
  13. Microsomal triglyceride transfer protein enhances cellular cholesteryl esterification by relieving product inhibition. Iqbal, J., Rudel, L.L., Hussain, M.M. J. Biol. Chem. (2008) [Pubmed]
  14. Microsomal triglyceride transfer protein expression in mouse intestine. Swift, L.L., Jovanovska, A., Kakkad, B., Ong, D.E. Histochem. Cell Biol. (2005) [Pubmed]
  15. Subcellular localization of microsomal triglyceride transfer protein. Swift, L.L., Zhu, M.Y., Kakkad, B., Jovanovska, A., Neely, M.D., Valyi-Nagy, K., Roberts, R.L., Ong, D.E., Jerome, W.G. J. Lipid Res. (2003) [Pubmed]
  16. The low density lipoprotein receptor prevents secretion of dense apoB100-containing lipoproteins from the liver. Larsson, S.L., Skogsberg, J., Björkegren, J. J. Biol. Chem. (2004) [Pubmed]
  17. Apolipoprotein B-related gene expression and ultrastructural characteristics of lipoprotein secretion in mouse yolk sac during embryonic development. Terasawa, Y., Cases, S.J., Wong, J.S., Jamil, H., Jothi, S., Traber, M.G., Packer, L., Gordon, D.A., Hamilton, R.L., Farese, R.V. J. Lipid Res. (1999) [Pubmed]
  18. Eliminating atherogenesis in mice by switching off hepatic lipoprotein secretion. Lieu, H.D., Withycombe, S.K., Walker, Q., Rong, J.X., Walzem, R.L., Wong, J.S., Hamilton, R.L., Fisher, E.A., Young, S.G. Circulation (2003) [Pubmed]
  19. Microsomal triglyceride transfer protein expression during mouse development. Shelton, J.M., Lee, M.H., Richardson, J.A., Patel, S.B. J. Lipid Res. (2000) [Pubmed]
  20. Progress towards understanding the role of microsomal triglyceride transfer protein in apolipoprotein-B lipoprotein assembly. Gordon, D.A., Jamil, H. Biochim. Biophys. Acta (2000) [Pubmed]
  21. Microsomal triglyceride transfer protein lipidation and control of CD1d on antigen-presenting cells. Dougan, S.K., Salas, A., Rava, P., Agyemang, A., Kaser, A., Morrison, J., Khurana, A., Kronenberg, M., Johnson, C., Exley, M., Hussain, M.M., Blumberg, R.S. J. Exp. Med. (2005) [Pubmed]
 
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