TY - JOUR
T1 - Phenotypic characterization of Lith genes that determine susceptibility to cholesterol cholelithiasis in inbred mice
T2 - Soluble pronucleating proteins in gallbladder and hepatic biles
AU - Van Erpecum, Karel J.
AU - Wang, David Q.H.
AU - Lammert, Frank
AU - Paigen, Beverly
AU - Groen, Albert K.
AU - Carey, Martin C.
N1 - Funding Information:
The authors thank Monika R. Leonard, Kam S. Mok, Michel J.A. van Wijland, Willem Renooij, Martin de Smet and Gerard P. van Berge Henegouwen for their advice and support. K.J.v.E. was a fellow of the Royal Netherlands Academy of Arts and Sciences (Koninklijke Nederlandse Academie van Wetenschappen) and was supported by grants of the Netherlands Organization of Scientific Research (Nederlandse Organisatie voor Wetenschappelijk Onderzoek) and the Fulbright Foundation. D.Q.-H.W. is a recipient of a New Scholar Award from the Ellison Medical Foundation (1999–2002). F.L. was supported by the Deutsche Forschungsgemeinschaft (La 997/3-1) and a career development grant from Ministerium für Schule und Weiterbildung, Wissenschaft und Forschung (NRW). This work was funded in part, by the following grants from the National Institutes of Health (US Public Health Service): DK 54012 to D.Q.-H.W., DK 51568 to B.P. and DK 52911, DK36588 and DK34854 to M.C.C.
PY - 2001
Y1 - 2001
N2 - Background/Aims: Gallstone susceptibility is high in C57L inbred mice (males > females) and low in AKR mice, related to variant lithogenic (Lith) genes. We examined the relationship between biliary crystallization-promoting proteins 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 increased markedly in males, but remained low in females of both strains and correlated with the cholesterol saturation index (CSI). In all groups, IgA and IgM concentrations decreased initially, but increased at later stages. There were no consistent changes in IgG concentrations, but aminopeptidase-N levels were higher in AKR than in C57L. During the lithogenic diet period, the CSI was ≥ 2 in C57L males, ≅ 1.5 in AKR males, and ≅ 1 in females of both strains. Taurodeoxycholate and taurochenodeoxycholate rose sharply in C57L, but remained low in AKR. Conclusions: Hydrophobic bile salts, cholesterol supersaturation, and possibly, 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 (Gastroenterology 2001;120:221).
AB - Background/Aims: Gallstone susceptibility is high in C57L inbred mice (males > females) and low in AKR mice, related to variant lithogenic (Lith) genes. We examined the relationship between biliary crystallization-promoting proteins 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 increased markedly in males, but remained low in females of both strains and correlated with the cholesterol saturation index (CSI). In all groups, IgA and IgM concentrations decreased initially, but increased at later stages. There were no consistent changes in IgG concentrations, but aminopeptidase-N levels were higher in AKR than in C57L. During the lithogenic diet period, the CSI was ≥ 2 in C57L males, ≅ 1.5 in AKR males, and ≅ 1 in females of both strains. Taurodeoxycholate and taurochenodeoxycholate rose sharply in C57L, but remained low in AKR. Conclusions: Hydrophobic bile salts, cholesterol supersaturation, and possibly, 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 (Gastroenterology 2001;120:221).
KW - Bile
KW - Bile salts
KW - Gallbladder
KW - Gallstone
KW - Hepatic
KW - Mouse
KW - Protein
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U2 - 10.1016/S0168-8278(01)00173-8
DO - 10.1016/S0168-8278(01)00173-8
M3 - Article
C2 - 11682027
AN - SCOPUS:0034799084
SN - 0168-8278
VL - 35
SP - 444
EP - 451
JO - Journal of Hepatology
JF - Journal of Hepatology
IS - 4
ER -