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Gene Review

Slc10a2  -  solute carrier family 10, member 2

Mus musculus

Synonyms: ASBT, Apical sodium-dependent bile acid transporter, IBAT, ISBT, Ileal Na(+)/bile acid cotransporter, ...
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Disease relevance of Slc10a2

  • On a low fat diet, the Slc10a2-/- mice did not have steatorrhea [1].
  • These findings indicate that bile acid malabsorption in cystic fibrosis is not caused by a decrease in IBAT activity at the brush border [2].
  • These results suggest that specific inhibition of ASBT is a novel therapeutic approach for treatment of hypercholesterolemia resulting in a decreased risk for atherosclerosis [3].
  • Here we show using retrograde transsynaptic tracing with attenuated pseudorabies virus coupled with dual-label immunohistochemistry that specific subsets of MC4R-expressing neurons in multiple nuclei of the central nervous system known to regulate sympathetic outflow polysynaptically connect with interscapular BAT (IBAT) [4].
  • In less severe forms of obesity, as found in the tubby and carboxypeptidase (Cpe)fat mice, and in diet-induced obese B6 mice, beta3AR expression was decreased in WAT by up to 90%, with more modest decreases in interscapular BAT (IBAT) [5].

High impact information on Slc10a2

  • RESULTS: In Caco-2 cells, ASBT messenger RNA expression was reduced 65% after interleukin-1beta treatment, while c-fos and c-jun were up-regulated 2-fold [6].
  • METHODS: Transient transfection studies of the human, mouse, and rat ASBT promoters and Northern analyses were performed in cells treated with the inflammatory cytokines and/or various activator protein-1 constructs [6].
  • Atorvastatin significantly increased Oatp2, Mdr2, and Asbt, while other transporters and enzymes were moderately affected [7].
  • The two subunits of the transporter were expressed together in human small intestine, kidney, and liver, tissues that also express the apical sodium-dependent bile acid uptake transporter ASBT (SLC10A2) [8].
  • Bile acids are transported across the ileal enterocyte brush border membrane by the well characterized apical sodium-dependent bile acid transporter (Asbt) Slc10a2; however, the carrier(s) responsible for transporting bile acids across the ileocyte basolateral membrane into the portal circulation have not been fully identified [9].

Biological context of Slc10a2


Anatomical context of Slc10a2

  • These results demonstrate that the mouse Ostalpha-Ostbeta heteromeric transporter is a basolateral bile acid carrier and may be responsible for bile acid efflux in ileum and other ASBT-expressing tissues [9].
  • By Northern blot analysis, Ostalpha and Ostbeta mRNA was detected only in mouse kidney and intestine, mirroring the horizontal gradient of expression of Asbt in the gastrointestinal tract [9].
  • Mouse ileal sodium dependent bile acid transporter (ISBT) was characterized using isolated enterocytes [13].
  • Both BAPA-3 and BAPA-6 inhibited Na(+)-dependent taurocholate (TC) uptake by Xenopus laevis oocytes expressing rat Asbt, with K(i) values of 28 and 16muM, respectively [14].
  • Experiments were repeated in a murine model transgenic for the green fluorescent protein to verify donor origin of the engrafted mucosa expressing IBAT [15].

Associations of Slc10a2 with chemical compounds

  • Liver cholesteryl ester content was reduced by 50% in Slc10a2-/- mice, and unexpectedly plasma high density lipoprotein cholesterol levels were slightly elevated [1].
  • Despite increased bile acid synthesis, the bile acid pool size was decreased by 80% and selectively enriched in cholic acid in the Slc10a2-/- mice [1].
  • The residual response in Cftr-null mice could be attributed to electrogenic ASBT activity, as it matched the TC-coupled absorptive Na+ flux [16].
  • All cysteines of mouse ileal and hepatic sodium-dependent bile acid transporters (Isbt and Ntcp, respectively) were individually replaced by alanine [17].
  • The effect of cold stimulation on the activity of sympathetic nerves running along blood vessels in interscapular, brown adipose tissues (IBAT) and skin overlying IBAT was examined in 15, urethane-anesthetized, artificially ventilated, C57BL/6J mice [18].

Other interactions of Slc10a2


Analytical, diagnostic and therapeutic context of Slc10a2

  • Simultaneously, adjacent segments of terminal ileum were taken and processed for immunohistochemistry and Western blots using an antibody against the IBAT protein [2].
  • CONCLUSIONS: Orthotopic transplantation of epithelial organoids containing ileal stem cells was used to generate a neoileal mucosa that expressed all 4 intestinal lineages along with a new zone of active bile acid uptake and IBAT expression in a recipient jejunal segment [15].
  • Our data confirm previous findings that adrenalectomy results in increased GDP binding to mitochondria from IBAT [20].
  • Cholangiocyte bile salt transporter mRNAs (apical sodium-dependent bile-salt transporter [Asbt] and multidrug resistance protein 3 [Mrp3]) were determined by reverse transcription-polymerase chain reaction (RT-PCR) [21].
  • Blood flow in the IBAT increased significantly following the stimulation; however, this effect was abolished by the denervation [18].


  1. Targeted deletion of the ileal bile acid transporter eliminates enterohepatic cycling of bile acids in mice. Dawson, P.A., Haywood, J., Craddock, A.L., Wilson, M., Tietjen, M., Kluckman, K., Maeda, N., Parks, J.S. J. Biol. Chem. (2003) [Pubmed]
  2. Ileal mucosal bile acid absorption is increased in Cftr knockout mice. Stelzner, M., Somasundaram, S., Lee, S.P., Kuver, R. BMC gastroenterology [electronic resource]. (2001) [Pubmed]
  3. Inhibition of ileal bile acid transport and reduced atherosclerosis in apoE-/- mice by SC-435. Bhat, B.G., Rapp, S.R., Beaudry, J.A., Napawan, N., Butteiger, D.N., Hall, K.A., Null, C.L., Luo, Y., Keller, B.T. J. Lipid Res. (2003) [Pubmed]
  4. Role of the central melanocortin circuitry in adaptive thermogenesis of brown adipose tissue. Voss-Andreae, A., Murphy, J.G., Ellacott, K.L., Stuart, R.C., Nillni, E.A., Cone, R.D., Fan, W. Endocrinology (2007) [Pubmed]
  5. Depressed expression of adipocyte beta-adrenergic receptors is a common feature of congenital and diet-induced obesity in rodents. Collins, S., Daniel, K.W., Rohlfs, E.M. Int. J. Obes. Relat. Metab. Disord. (1999) [Pubmed]
  6. c-Fos is a critical mediator of inflammatory-mediated repression of the apical sodium-dependent bile acid transporter. Neimark, E., Chen, F., Li, X., Magid, M.S., Alasio, T.M., Frankenberg, T., Sinha, J., Dawson, P.A., Shneider, B.L. Gastroenterology (2006) [Pubmed]
  7. CAR and PXR agonists stimulate hepatic bile acid and bilirubin detoxification and elimination pathways in mice. Wagner, M., Halilbasic, E., Marschall, H.U., Zollner, G., Fickert, P., Langner, C., Zatloukal, K., Denk, H., Trauner, M. Hepatology (2005) [Pubmed]
  8. OSTalpha-OSTbeta: a major basolateral bile acid and steroid transporter in human intestinal, renal, and biliary epithelia. Ballatori, N., Christian, W.V., Lee, J.Y., Dawson, P.A., Soroka, C.J., Boyer, J.L., Madejczyk, M.S., Li, N. Hepatology (2005) [Pubmed]
  9. The heteromeric organic solute transporter alpha-beta, Ostalpha-Ostbeta, is an ileal basolateral bile acid transporter. Dawson, P.A., Hubbert, M., Haywood, J., Craddock, A.L., Zerangue, N., Christian, W.V., Ballatori, N. J. Biol. Chem. (2005) [Pubmed]
  10. Localization of the ileal sodium-bile salt cotransporter gene (Slc10a2) to mouse chromosome 8. Lammert, F., Paigen, B., Carey, M.C. Mamm. Genome (1998) [Pubmed]
  11. Single and interacting QTLs for cholesterol gallstones revealed in an intercross between mouse strains NZB and SM. Lyons, M.A., Korstanje, R., Li, R., Sheehan, S.M., Walsh, K.A., Rollins, J.A., Carey, M.C., Paigen, B., Churchill, G.A. Mamm. Genome (2005) [Pubmed]
  12. Coordinate regulation of bile acid biosynthetic and recovery pathways. Torchia, E.C., Cheema, S.K., Agellon, L.B. Biochem. Biophys. Res. Commun. (1996) [Pubmed]
  13. Characterization, cDNA cloning, and functional expression of mouse ileal sodium-dependent bile acid transporter. Saeki, T., Matoba, K., Furukawa, H., Kirifuji, K., Kanamoto, R., Iwami, K. J. Biochem. (1999) [Pubmed]
  14. Inhibition of the intestinal absorption of bile acids using cationic derivatives: Mechanism and repercussions. Vicens, M., Macias, R.I., Briz, O., Rodriguez, A., El-Mir, M.Y., Medarde, M., Marin, J.J. Biochem. Pharmacol. (2007) [Pubmed]
  15. Orthotopic transplantation of intestinal mucosal organoids in rodents. Avansino, J.R., Chen, D.C., Hoagland, V.D., Woolman, J.D., Stelzner, M. Surgery (2006) [Pubmed]
  16. Activation of CFTR by ASBT-mediated bile salt absorption. Bijvelds, M.J., Jorna, H., Verkade, H.J., Bot, A.G., Hofmann, F., Agellon, L.B., Sinaasappel, M., de Jonge, H.R. Am. J. Physiol. Gastrointest. Liver Physiol. (2005) [Pubmed]
  17. Effects of Cys mutation on taurocholic acid transport by mouse ileal and hepatic sodium-dependent bile acid transporters. Saeki, T., Kuroda, T., Matsumoto, M., Kanamoto, R., Iwami, K. Biosci. Biotechnol. Biochem. (2002) [Pubmed]
  18. Responses of sympathetic nerves innervating blood vessels in interscapular, brown adipose tissue and skin during cold stimulation in anesthetized C57BL/6J mice. Engel, B.T., Sato, A., Sato, Y. Jpn. J. Physiol. (1992) [Pubmed]
  19. Ontogenetic development and spatial distribution of the ileal apical sodium-dependent bile acid transporter and the ileal lipid-binding protein in apoE knockout and C57BL/6 mice. Håkansson, P., Andersson, I., Nyström, S., Löfgren, L., Amrot, L.F., Li, H. Scand. J. Gastroenterol. (2002) [Pubmed]
  20. Adrenalectomy in genetically obese ob/ob and db/db mice increases the proton conductance pathway. Shargill, N.S., Lupien, J.R., Bray, G.A. Horm. Metab. Res. (1989) [Pubmed]
  21. Partial characterization of cytoprotective mechanisms of lecithin against bile salt-induced bile duct damage. Tsuboi, K., Tazuma, S., Nishioka, T., Chayama, K. J. Gastroenterol. (2004) [Pubmed]
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