Murine model of long-term obstructive jaundice

Abstract

Background With the recent emergence of conjugated bile acids as signaling molecules in cancer, a murine model of obstructive jaundice by cholestasis with long-term survival is in need. Here, we investigated the characteristics of 3 murine models of obstructive jaundice. Methods C57BL/6J mice were used for total ligation of the common bile duct (tCL), partial common bile duct ligation (pCL), and ligation of left and median hepatic bile duct with gallbladder removal (LMHL) models. Survival was assessed by Kaplan-Meier method. Fibrotic change was determined by Masson-Trichrome staining and Collagen expression. Results 70% (7/10) of tCL mice died by Day 7, whereas majority 67% (10/15) of pCL mice survived with loss of jaundice. 19% (3/16) of LMHL mice died; however, jaundice continued beyond Day 14, with survival of more than a month. Compensatory enlargement of the right lobe was observed in both pCL and LMHL models. The pCL model demonstrated acute inflammation due to obstructive jaundice 3 days after ligation but jaundice rapidly decreased by Day 7. The LHML group developed portal hypertension as well as severe fibrosis by Day 14 in addition to prolonged jaundice. Conclusion The standard tCL model is too unstable with high mortality for long-term studies. pCL may be an appropriate model for acute inflammation with obstructive jaundice but long term survivors are no longer jaundiced. The LHML model was identified to be the most feasible model to study the effect of long-term obstructive jaundice.

C/EBP homologous protein–induced loss of intestinal epithelial stemness contributes to bile duct ligation–induced cholestatic liver injury in mice

“…C57BL/6J wild‐type (WT) mice and CHOP −/− mice (both male and female, 8‐10 weeks old) were purchased from The Jackson Laboratory (Bar Harbor, ME) and housed under a 12‐hour light/12‐hour dark cycle with free access to water and normal chow. BDL or sham operation was performed on WT and CHOP −/− mice as described for 1, 3, 5, 7, or 14 days . At the end of the experiment, the mice were sacrificed for further studies.…”

Distinct roles of ecto-nucleoside triphosphate diphosphohydrolase-2 (NTPDase2) in liver regeneration and fibrosis

“…As NTPDase2 was previously shown to be downregulated in bile duct ligated liver tissue, and given the higher mortality and inconsistency of this experimental model [34], we chose DDC feeding as an additional model for liver fibrosis induced by cholestasis and biliary inflammation [35]. We demonstrate a b Fig.…”

Murine breast cancer mastectomy model that predicts patient outcomes for drug development

“…For the last decade, our laboratory has been studying murine cancer models that mimic human cancer progression for use in preclinical trials (4–6, 10, 11, 13, 20). The purpose of murine models in preclinical trials is to predict whether a novel therapeutic agent will demonstrate efficacy in humans (2–5, 7).…”

“…8 days after inoculation, either tumorectomy or Halsted mastectomy were performed (n = 7, each). Resected tumor weight, bioluminescence on the day after tumor removal, and recurrence rate were compared between these two procedures using previously reported techniques (4, 6, 10–13). …”