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Gene Review

Lith1  -  lithogenic gene 1

Mus musculus

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Disease relevance of Lith1


Psychiatry related information on Lith1


High impact information on Lith1

  • Analysis of mice on either the chow or the lithogenic diet revealed that CCK-1R(-/-) animals had larger gallbladder volumes (predisposing to bile stasis), significant retardation of small-intestinal transit times (resulting in increased cholesterol absorption), and increased biliary cholesterol secretion rates [7].
  • We measured several parameters of cholesterol metabolism, fatty acid synthesis, and biliary lipid levels in mice fed a normal or a lithogenic diet [8].
  • The incidence of gallstones decreased from 90% in control mice to 33% in Mttp(Delta/Delta) mice after 8 weeks of a lithogenic diet (P < .0001) [8].
  • Quantitative trait locus (QTL) mapping was employed to identify Lith loci in mice [9].
  • Because mouse and human genomes are conserved and only a critical subset of homologous genes appears rate limiting for gallstone susceptibility in these species, a genetic map of mouse lithogenic (Lith) loci provides a "roadmap" for the discovery of human LITH genes [9].

Chemical compound and disease context of Lith1


Biological context of Lith1


Anatomical context of Lith1


Associations of Lith1 with chemical compounds


Regulatory relationships of Lith1

  • TTR-Abcb11 and FVB/NJ strain control mice were fed a lithogenic or chow diet and cholesterol crystal and gallstone formation were measured [26].
  • In inbred mice gallstone susceptibility is determined by Lith (lithogenic) genes which promote cholesterol hypersecretion in bile as a response to a high-fat diet [27].
  • HL knockout mice had a similar prevalence of gallstone formation as compared with control mice when both strains were fed with a lithogenic diet [28].

Other interactions of Lith1

  • In response to the lithogenic diet, Bsep (Abcb11) protein expression was up-regulated only marginally and bile salt secretion did not increase [29].
  • When examined after 6 weeks on the lithogenic diet, the activity of hepatic 3-hydroxy-3-methylglutaryl-CoA reductase (EC was downregulated as expected in the gallstone-resistant strains, AKR and SJL, but this enzyme failed to downregulate in C57L and SWR, the gallstone-susceptible strains [15].
  • In response to the lithogenic diet, a greater reduction in cholesterol 7alpha-hydroxylase activity in Pctp-/- mice could be attributed to increased size and hydrophobicity of the bile salt pool [30].
  • Basal expression of hepatic SR-BI protein was dissimilar in both wild-type and SR-BI mice, and remained unaltered in response to the lithogenic diet [31].
  • Male agouti mice of the same age did not form gallstones until they had consumed the lithogenic food for 8 weeks [32].

Analytical, diagnostic and therapeutic context of Lith1


  1. Interacting QTLs for cholesterol gallstones and gallbladder mucin in AKR and SWR strains of mice. Wittenburg, H., Lammert, F., Wang, D.Q., Churchill, G.A., Li, R., Bouchard, G., Carey, M.C., Paigen, B. Physiol. Genomics (2002) [Pubmed]
  2. Phenotypic characterization of Lith genes that determine susceptibility to cholesterol cholelithiasis in inbred mice: physical-chemistry of gallbladder bile. Wang, D.Q., Paigen, B., Carey, M.C. J. Lipid Res. (1997) [Pubmed]
  3. Identification of cholelithogenic enterohepatic helicobacter species and their role in murine cholesterol gallstone formation. Maurer, K.J., Ihrig, M.M., Rogers, A.B., Ng, V., Bouchard, G., Leonard, M.R., Carey, M.C., Fox, J.G. Gastroenterology (2005) [Pubmed]
  4. Restoration of gallstone susceptibility by leptin in C57BL/6J ob/ob mice. Hyogo, H., Roy, S., Cohen, D.E. J. Lipid Res. (2003) [Pubmed]
  5. Helicobacter pylori and cholesterol gallstone formation in C57L/J mice: a prospective study. Maurer, K.J., Rogers, A.B., Ge, Z., Wiese, A.J., Carey, M.C., Fox, J.G. Am. J. Physiol. Gastrointest. Liver Physiol. (2006) [Pubmed]
  6. Changes in bile composition during gallstone formation in hamsters. Yanaura, S., Iizuka, A. J. Pharmacobio-dyn. (1981) [Pubmed]
  7. Targeted disruption of the murine cholecystokinin-1 receptor promotes intestinal cholesterol absorption and susceptibility to cholesterol cholelithiasis. Wang, D.Q., Schmitz, F., Kopin, A.S., Carey, M.C. J. Clin. Invest. (2004) [Pubmed]
  8. Inactivation of hepatic microsomal triglyceride transfer protein protects mice from diet-induced gallstones. Amigo, L., Castro, J., Miquel, J.F., Zanlungo, S., Young, S., Nervi, F. Gastroenterology (2006) [Pubmed]
  9. Cholesterol Gallstone Susceptibility Loci: A Mouse Map, Candidate Gene Evaluation, and Guide to Human LITH Genes. Lyons, M.A., Wittenburg, H. Gastroenterology (2006) [Pubmed]
  10. Phenotypic characterization of Lith genes that determine susceptibility to cholesterol cholelithiasis in inbred mice: integrated activities of hepatic lipid regulatory enzymes. Lammert, F., Wang, D.Q., Paigen, B., Carey, M.C. J. Lipid Res. (1999) [Pubmed]
  11. Estrogen receptor alpha, but not beta, plays a major role in 17beta-estradiol-induced murine cholesterol gallstones. Wang, H.H., Afdhal, N.H., Wang, D.Q. Gastroenterology (2004) [Pubmed]
  12. Cholesterol synthesis inhibition distal to squalene upregulates biliary phospholipid secretion and counteracts cholelithiasis in the genetically prone C57L/J mouse. Clarke, G.A., Bouchard, G., Paigen, B., Carey, M.C. Gut (2004) [Pubmed]
  13. Differential effects of ursodeoxycholic acid and ursocholic acid on the formation of biliary cholesterol crystals in mice. Uchida, K., Akiyoshi, T., Igimi, H., Takase, H., Nomura, Y., Ishihara, S. Lipids (1991) [Pubmed]
  14. The prevention of experimental cholesterol gallstones by ileectomy in mice. Yamamoto, T., Yamamoto, M., Ohyanagi, H., Saitoh, Y., Akiyoshi, T., Uchida, K. The Japanese journal of surgery. (1988) [Pubmed]
  15. Lith1, a major gene affecting cholesterol gallstone formation among inbred strains of mice. Khanuja, B., Cheah, Y.C., Hunt, M., Nishina, P.M., Wang, D.Q., Chen, H.W., Billheimer, J.T., Carey, M.C., Paigen, B. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  16. Association of a lithogenic Abcg5/Abcg8 allele on Chromosome 17 (Lith9) with cholesterol gallstone formation in PERA/EiJ mice. Wittenburg, H., Lyons, M.A., Li, R., Kurtz, U., Mössner, J., Churchill, G.A., Carey, M.C., Paigen, B. Mamm. Genome (2005) [Pubmed]
  17. Genetic analysis of cholesterol gallstone formation: searching for Lith (gallstone) genes. Wang, D.Q., Afdhal, N.H. Current gastroenterology reports. (2004) [Pubmed]
  18. Biliary cholesterol hypersecretion in gallstone-susceptible mice is associated with hepatic up-regulation of the high-density lipoprotein receptor SRBI. Fuchs, M., Ivandic, B., Müller, O., Schalla, C., Scheibner, J., Bartsch, P., Stange, E.F. Hepatology (2001) [Pubmed]
  19. DNA synthesis, cell proliferation index in normal and abnormal gallbladder epithelium. Lamote, J., Willems, G. Microsc. Res. Tech. (1997) [Pubmed]
  20. Morphological alterations in epithelial cells of the mouse gallbladder 30 hours after treatment with lithogenic diet. Ziegler, U., Palme, G., Merker, H.J. Pathol. Res. Pract. (1982) [Pubmed]
  21. Alterations in hepatocytes of mice fed a gallstone-inducing diet: occurrence of nuclear and cytoplasmic lipids. Saland, L.C., Napolitano, L.M. Anat. Rec. (1979) [Pubmed]
  22. Synthesis of glycoproteins in the Golgi complex of the mouse gallbladder epithelium during fasting, refeeding, and gallstone formation. A light microscopic autoradiographic and quantitative electron microscopic study. Wahlin, T. Histochemistry (1977) [Pubmed]
  23. Hepatic overexpression of murine Abcb11 increases hepatobiliary lipid secretion and reduces hepatic steatosis. Figge, A., Lammert, F., Paigen, B., Henkel, A., Matern, S., Korstanje, R., Shneider, B.L., Chen, F., Stoltenberg, E., Spatz, K., Hoda, F., Cohen, D.E., Green, R.M. J. Biol. Chem. (2004) [Pubmed]
  24. Effect of Beta-sitosterol on cholesterol-cholic acid-induced gallstone formation in mice. Goswami, S.K., Frey, C.F. Am. J. Gastroenterol. (1976) [Pubmed]
  25. Review: pathogenesis of gallstones. Dowling, R.H. Aliment. Pharmacol. Ther. (2000) [Pubmed]
  26. Mice overexpressing hepatic Abcb11 rapidly develop cholesterol gallstones. Henkel, A., Wei, Z., Cohen, D.E., Green, R.M. Mamm. Genome (2005) [Pubmed]
  27. Cholelithiasis: genetic hypothesis. Sanchez-Mete, L., Attili, A.F. Minerva gastroenterologica e dietologica. (2000) [Pubmed]
  28. Biliary lipid secretion, bile acid metabolism, and gallstone formation are not impaired in hepatic lipase-deficient mice. Amigo, L., Mardones, P., Ferrada, C., Zanlungo, S., Nervi, F., Miquel, J.F., Rigotti, A. Hepatology (2003) [Pubmed]
  29. Expression of liver plasma membrane transporters in gallstone-susceptible and gallstone-resistant mice. Müller, O., Schalla, C., Scheibner, J., Stange, E.F., Fuchs, M. Biochem. J. (2002) [Pubmed]
  30. Altered hepatic cholesterol metabolism compensates for disruption of phosphatidylcholine transfer protein in mice. Wu, M.K., Cohen, D.E. Am. J. Physiol. Gastrointest. Liver Physiol. (2005) [Pubmed]
  31. Susceptibility to murine cholesterol gallstone formation is not affected by partial disruption of the HDL receptor SR-BI. Wang, D.Q., Carey, M.C. Biochim. Biophys. Acta (2002) [Pubmed]
  32. Different susceptibilities to the formation of cholesterol gallstones in mice. Alexander, M., Portman, O.W. Hepatology (1987) [Pubmed]
  33. Lith genes control mucin accumulation, cholesterol crystallization, and gallstone formation in A/J and AKR/J inbred mice. Lammert, F., Wang, D.Q., Wittenburg, H., Bouchard, G., Hillebrandt, S., Taenzler, B., Carey, M.C., Paigen, B. Hepatology (2002) [Pubmed]
  34. Effects of gallstone-promoting diet and vagotomy on the mouse gallbladder epithelium. Axelsson, H.G. Hepatogastroenterology (1999) [Pubmed]
  35. Effects of fatty acid bile acid conjugates (FABACs) on biliary lithogenesis: Ppotential consequences for non-surgical treatment of gallstones. Konikoff, F.M., Gilat, T. Curr. Drug Targets Immune Endocr. Metabol. Disord. (2005) [Pubmed]
  36. Biliary proteins from hepatic bile of rats fed curcumin or capsaicin inhibit cholesterol crystal nucleation in supersaturated model bile. Hussain, M.S., Chandrasekhara, N. Indian J. Biochem. Biophys. (1994) [Pubmed]
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