Phenotypic characterization of Lith genes that determine susceptibility tocholesterol cholelithiasis in inbred mice: soluble pronucleating proteins in gallbladder and hepatic biles

Background/Aims: Gallstone susceptibility is high in C57L inbred mice (male s > females) and low in AKR mice, related to variant lithogenic (Lith) gene s. We examined the relationship between biliary crystallization-promoting p roteins and gallstone susceptibility. Methods: Biliary protein and lipid concentrations were determined at 0, 7, 14, 21, 28 and 56 days on a lithogenic diet. Results: Protein and soluble mucin concentrations in gallbladder biles incr eased markedly in males, but remained low in females of both strains and co rrelated with the cholesterol saturation index (CST). In all groups, IgA an d IgM concentrations decreased initially, but increased at later stages. Th ere were no consistent changes in IgG concentrations, but aminopeptidase-N levels were higher in AKR than in C57L. During the lithogenic diet period, the CST was greater than or equal to 2 in C57L males, approximate to 1.5 in AKR males, and approximate to I in females of both strains. Taurodeoxychol ate and taurochenodeoxycholate rose sharply in C57L, but remained low in AK R. Conclusions: Hydrophobic bile salts, cholesterol supersaturation, and possi bly, high mucin concentrations are associated with gallstone formation. In vitro crystallization-promoting immunoglobulins and aminopeptidase-N do not appear to be major factors in murine gallstone pathogenesis, in line with the observation that genes encoding these proteins do not co-localize with any known Lith locus (C) 2001 European Association for the Study of the Liv er. Published by Elsevier Science BN. All rights reserved.