Gallbladder histopathology during murine gallstone formation: Relation to motility and concentrating function

Karel J. Van Erpecum, David Q.H. Wang, Antonio Moschetta, Domenico Ferri, Maria Svelto, Piero Portincasa, Jan Jaap Hendrickx, Marguérite Schipper, Giuseppe Calamita

Research output: Contribution to journalArticlepeer-review

69 Scopus citations


C57L mice are susceptible and AKR mice are resistant to gallstone formation. We studied in male mice of both strains gallbladder histopathology, cholecystokinin-induced emptying, and concentrating function at 0, 14, 28, and 56 days on a lithogenic diet. Gallbladder wall thickness increased on the diet, with stromal granulocyte infiltration, progressive fibrosis, edema, and epithelial cell indentation, particularly in C57L. Strong basal cholecystokinin octapeptide-induced gallbladder emptying (70% of fasting volumes) occurred in both strains, but fasting gallbladder volumes were significantly larger in C57L (14.8 ± 2.2 μl vs. 8.8 ± 1.0 ml). On the diet, fasting volumes increased exclusively in C57L (28.6 ± 2.9 μl on day 56), with progressively decreased emptying (27% of fasting volumes on day 56). Gallbladder emptying remained normal in AKR. Gallbladder concentrating function decreased on the lithogenic diet (especially in C57L), coinciding with decreased aquaporin-1 (AQP1) and AQP8 expression at the mRNA and protein levels. In additional experiments, similar downregulation of AQP1 and AQP8 mRNA expression occurred in farnesoid X receptor (FXR)-deficient mice after 1 week on the lithogenic diet, without any difference from corresponding wild-type mice. In conclusion, during murine lithogenesis, altered gallbladder histology is associated with impaired motility, reduced concentrating function, and decreased AQP1 and AQP8 expression, the latter without the involvement of the FXR.

Original languageEnglish (US)
Pages (from-to)32-41
Number of pages10
JournalJournal of Lipid Research
Issue number1
StatePublished - Jan 2006
Externally publishedYes


  • Aquaporin
  • Cholesterol
  • Farnesoid X receptor
  • Gallbladder emptying
  • Water channel

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology


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