Disease relevance of Abcg5

• An infusion of increasing amounts of the hydrophobic BS taurodeoxycholate increased cholesterol excretion by 3.0- and 2.4-fold in wild-type and Abcg5(-/-) mice but rapidly induced cholestasis in Abcg5(-/-) mice [1].

High impact information on Abcg5

• Hepatic expression of Abcg8 was reduced by about 35% in Abcg5-deficient mice when compared with controls [2].
• Surprisingly, high plasma beta-sitosterol and campesterol concentrations were even further elevated in Abcg5-null mice on treatment with the synthetic LXR agonist T0901317 (0.015% dietary supplementation, 10 days), whereas these concentrations were reduced by approximately 75% in wild-type mice [2].
• CONCLUSIONS: Our data show that disruption of the Abcg5 gene alone is sufficient to cause hyperabsorption of dietary plant sterols and sitosterolemia in mice, whereas the ability to secrete cholesterol into bile is maintained [2].
• METHODS: To test whether deficiency of ABCG5 alone is sufficient to induce sitosterolemia, Abcg5-null mice were generated and characterized with respect to sterol metabolism [2].
• RESULTS: Abcg5 deficiency was associated with strongly elevated plasma levels of beta-sitosterol (37-fold) and campesterol (7.7-fold) as well as reduced plasma cholesterol concentrations (-40%) [2].

Biological context of Abcg5

• A significant locus associated with gallstone score on chromosome 17, named Lith9 (susceptibility allele conferred by strain PERA/Ei), colocalizes with the genes Abcg5 and Abcg8 that encode the canalicular cholesterol transporter [3].
• Expression of Abcg5 and Abcg8, recently implicated in biliary excretion of cholesterol and its intestinal absorption, was induced in T0901317-treated mice [4].
• Analysis of the kinetics of cholesterol secretion suggested that diosgenin probably activates a step before Abcg5/g8 [5].
• Haplotype analysis narrowed this QTL, and sequencing of the candidate genes Abcg5 and Abcg8 confirmed shared alleles in strains I/LnJ and DBA/2J that differed from the alleles in strain PERA/EiJ [6].
• Plant sterol and stanol-induced reduction of cholesterol absorption in mice is not associated with upregulation of intestinal LXR target genes nor is it influenced by Abcg5-deficiency [7].

Anatomical context of Abcg5

• Livers and small intestines were harvested and expression levels of Abcg5, Abcg8 and Abcb4 were determined by real-time polymerase chain reaction [8].
• We found that Abcg5 and Abcg8 in the jejunum and ileum, but not in the duodenum, were main factors in determining, in part, variations in Ch absorption efficiency [9].

Associations of Abcg5 with chemical compounds

• Despite similar bile salt (BS) excretion rates, basal total sterol and phospholipid (PL) output rates were reduced by 82% and 35%, respectively, in chow-fed Abcg5(-/-) mice compared with wild-type mice [1].
• When mice were infused with the hydrophilic BS tauroursodeoxycholate, similar relative increases in bile flow, BS output, PL output, and total sterol output were observed in wild-type, Abcg5(+/-), and Abcg5(-/-) mice [1].
• The plant sterol diosgenin has been shown to stimulate biliary cholesterol secretion in mice without affecting the expression of the adenosine triphosphate-binding cassette transporter heterodimer Abcg5/g8 [5].
• Molecular cloning, genomic organization, genetic variations, and characterization of murine sterolin genes Abcg5 and Abcg8 [10].

Physical interactions of Abcg5

• Cholesterol absorption is mainly regulated by the jejunal and ileal ATP-binding cassette sterol efflux transporters Abcg5 and Abcg8 in mice [9].

Other interactions of Abcg5

• To elucidate the roles of ABCG5 and ABCG8 in the trafficking of sterols, we disrupted Abcg5 and Abcg8 in mice (G5G8(-/-)) [11].

References