Version of Record online: 27 MAY 2013
Copyright © 2013 American Association for the Study of Liver Diseases
Volume 58, Issue 1, pages 192–204, July 2013
How to Cite
Potikha, T., Stoyanov, E., Pappo, O., Frolov, A., Mizrahi, L., Olam, D., Shnitzer-Perlman, T., Weiss, I., Barashi, N., Peled, A., Sass, G., Tiegs, G., Poirier, F., Rabinovich, G. A., Galun, E. and Goldenberg, D. (2013), Interstrain differences in chronic hepatitis and tumor development in a murine model of inflammation-mediated hepatocarcinogenesis. Hepatology, 58: 192–204. doi: 10.1002/hep.26335
Potential conflict of interest: Nothing to report.
This study was supported by the Kamea Scientific Foundation of the Israeli Government (to Tamara Potikha and Daniel Goldenberg), by the Chief Scientist of the Israeli Ministry of Health (through grant 4930 to Daniel Goldenberg), by the German Research Foundation through SFB841 projects C2 (to Gabriele Sass and Gisa Tiegs) and C3 (to Eithan Galun), and by the Argentinean Agency for Science and Technology and Sales Foundation for Cancer (to Gabriel A. Rabinovich).
- Issue online: 24 JUN 2013
- Version of Record online: 27 MAY 2013
- Accepted manuscript online: 19 FEB 2013 09:52AM EST
- Manuscript Accepted: 10 FEB 2013
- Manuscript Received: 18 OCT 2012
Additional Supporting Information may be found in the online version of this article.
|HEP_26335_sm_SuppFig1.tif||10732K||Supporting Information Figure 1. Extensive bile duct proliferation and portal inflammation in the livers of Mdr2-KO mice at young age. (A) H&E staining of representative liver sections from Mdr2+/-/FVB, Mdr2-KO/FVB, Mdr2+/-/B6, and Mdr2-KO/B6 mice aged one (upper panels), two (middle panels) or three (bottom panels) months. Magnification x100. (B) F4/80 immunostaining for Mdr2-KO and control mice of both strains. Animal age and image magnification are as in (A). Higher F4/80 expression reflects higher infiltration of the monocytes/macrophages into Mdr2-KO compared to control Mdr2+/- livers starting from the first month of age. (C, D) Kinetics of T cells (C) and neutrophils (D) infiltration into the Mdr2-KO/FVB and Mdr2-KO/B6 livers. Staining with CD3-specific antibody reveals intense infiltration of T cells into portal tracts of the Mdr2-KO/FVB (left panel), and Mdr2-KO/B6 (right panel) livers. Staining with Ly-6B-specific antibody reveals intense infiltration of neutrophils into portal tracts of the Mdr2-KO/FVB (left panel), and Mdr2-KO/B6 livers (right panel). There was no T cell and neutrophil infiltration into the control livers (data not shown); animal age and image magnification – as in (A).|
|HEP_26335_sm_SuppFig2.tif||4926K||Supporting Information Figure 2. Higher BrdU incorporation into hepatocytes of Mdr2-KO mice compared to Mdr2+/- controls in both strains at early age. (A) BrdU incorporation in Mdr2+/- (top row), and Mdr2-KO (bottom row) livers of the FVB strain. (B) BrdU incorporation in Mdr2+/+ (top row), Mdr2+/- (middle row) and Mdr2-KO (bottom row) livers of the B6 strain. Magnification x100. For each group, four to eight mice were used at each time point.|
|HEP_26335_sm_SuppFig3.tif||8372K||Supporting Information Figure 3. Cyclin D1 is over-expressed in hepatocyte nuclei of Mdr2-KO mice of both strains. Liver tissue sections obtained from Mdr2-KO and control Mdr2+/- mice of the FVB (A) and B6 (B) strains were analyzed at the age of 1, 2 and 3 months and stained with the anti-cyclin D1 antibody. Magnification x100.|
|HEP_26335_sm_SuppFig4.tif||7155K||Supporting Information Figure 4. Rare apoptotic events of non-hepatic cells from control and mutant livers. TUNEL assay was performed on Mdr2+/-/FVB and Mdr2-KO/FVB liver sections to label apoptotic cells; cell nuclei were stained with DAPI (magnification x400). Left panel: TUNEL staining; middle panel: DAPI staining; right panel: overlay of both stainings. In the first month of age, an increased apoptosis of non-hepatic cells in the mutant livers was detected.|
|HEP_26335_sm_SuppFig5.tif||6526K||Supporting Information Figure 5. Expression of the Lipin-1 and Mbd1 proteins in the liver tumors of aged Mdr2-KO mice. IHC staining of the tumor (T) and non-tumor (NT) liver tissues from Mdr2-KO mice of the B6 (A, C) and FVB (B, D) genetic backgrounds. (A, B) Lipin-1 expression; (C, D) Mbd-1 expression. Mdr2-KO/B6 mice were 18 months-old, Mdr2-KO/FVB mice were 14 months-old. The different patterns of staining - higher in T compared to NT (left panel) or equal, or less in T compared to NT (right panel) - are presented for each strain. Magnification x100. Arrowheads show borders between T and NT tissues.|
|HEP_26335_sm_SuppTab1.doc||12K||Supporting Information Table 1. PCR primers used in this study.|
|HEP_26335_sm_SuppTab2.doc||39K||Supporting Information Table 2. Selected genes aberrantly expressed in the Mdr2-KO livers of only one of the FVB or B6 strains.|
|HEP_26335_sm_SuppTab3.doc||33K||Supporting Information Table 3. Selected genes aberrantly expressed in the Mdr2-KO livers of both FVB and B6 strains.|
|HEP_26335_sm_SuppTab4.doc||66K||Supporting Information Table 4. Known genotypic and phenotypic differences between FVB and B6 strains.|
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