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J Surg Res. 2016 Nov;206(1):118-125. doi: 10.1016/j.jss.2016.07.020. Epub 2016 Jul 18.

Murine model of long-term obstructive jaundice.

Author information

1
Division of Surgical Oncology, Department of Surgery, Virginia Commonwealth University School of Medicine, Richmond, Virginia; Department of Biochemistry and Molecular Biology, Virginia Commonwealth University School of Medicine, Richmond, Virginia.
2
Department of Microbiology and Immunology, Virginia Commonwealth University School of Medicine, Richmond, Virginia.
3
Division of Surgical Oncology, Department of Surgery, Virginia Commonwealth University School of Medicine, Richmond, Virginia.
4
Department of Biochemistry and Molecular Biology, Virginia Commonwealth University School of Medicine, Richmond, Virginia.
5
Division of Surgical Oncology, Department of Surgery, Virginia Commonwealth University School of Medicine, Richmond, Virginia; Department of Biochemistry and Molecular Biology, Virginia Commonwealth University School of Medicine, Richmond, Virginia; Division of Breast Surgery, Department of Surgical Oncology, Roswell Park Cancer Institute, Buffalo, New York. Electronic address: Kazuaki.takabe@roswellpark.org.

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 three 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:

Overall, 70% (7 of 10) of tCL mice died by day 7, whereas majority 67% (10 of 15) of pCL mice survived with loss of jaundice. A total of 19% (3 of 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 d after ligation but jaundice rapidly decreased by day 7. The LHML group developed portal hypertension and severe fibrosis by day 14 in addition to prolonged jaundice.

CONCLUSIONS:

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.

KEYWORDS:

Bile acid; Bile duct; Cholestasis; Mouse; Murine model; Obstructive jaundice; bile acid

PMID:
27916350
PMCID:
PMC5142243
DOI:
10.1016/j.jss.2016.07.020
[Indexed for MEDLINE]
Free PMC Article

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