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A reproducible and well-tolerated method for 2/3 partial hepatectomy in mice

Nature Protocols volume 3, pages 1167–1170 (2008)Cite this article

An Addendum to this article was published on 29 May 2014

This article has been updated

Abstract

The ability of hepatocytes to enter the cell cycle and regenerate the liver after tissue loss provides an in vivo model to study the regulation of proliferation and organ regeneration. The extent of hepatocyte proliferation is directly proportional to the amount of resected liver tissue, and 2/3 partial hepatectomy (2/3 PH) leads to highly synchronized hepatocyte cell-cycle entry and progression. This surgical technique was first described in rats and requires modification for application in mice. Lack of standardization of 2/3 PH in mice has caused discrepancies in the results obtained in different laboratories. Here, we provide a protocol and a movie describing a straightforward surgical technique, which takes 15–20 min, to consistently remove two-thirds of the liver in mice. As this protocol is not associated with mortality and gives highly reproducible results, we hope that it will be widely used and serve to standardize 2/3 PH in mice.

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Figure 1: Livers 48 h after 2/3 PH.
Figure 2: Extent of liver injury after 2/3 PH in animals anesthetized with different types of anesthetics (avertin, ketamine/xylazine or isoflurane).
Figure 3: Schematic drawings of mouse liver anatomy and positioning of silk threads for knots.
Figure 4: Kinetics of BrdU incorporation after 2/3 PH.

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Change history

  • 23 May 2014

     Pain management during mouse experimentation has improved in the past several years, thereby requiring an update to this protocol. Updated information has been appended to the PDF version of this article.

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Acknowledgements

H.W. and C.M. thank B. Rain Bennett (Flying Flounder Productions) and Dr. Susan Sunnarborg for helping with the production of the video. C.M. thanks Dr. Jose Luiz de Godoy for introducing her to the art of surgery and Dr. Nelson Fausto for his mentorship in the field of liver regeneration. H.W. is a Liver Scholar of the American Liver Foundation/American Society of Transplantation.

Author information

Authors and Affiliations

  1. Institut Cochin, Université Paris Descartes, CNRS (UMR 8104), Paris, France

    Claudia Mitchell

  2. Inserm (U567), 24, Rue du Faubourg St-Jacques, Paris, 75014, France

    Claudia Mitchell

  3. Institute for Regeneration Medicine and Department of Surgery, Division of Transplantation, University of California San Francisco, 513 Parnassus Avenue, San Francisco, 94143, California, USA

    Holger Willenbring

Authors
  1. Claudia Mitchell
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  2. Holger Willenbring
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Corresponding author

Correspondence to Claudia Mitchell.

Supplementary information

Supplementary Video 1

Step 3. Opening. (MOV 2853 kb)

Supplementary Video 2

Step 4. Liver exposure with rubber band. (MOV 1013 kb)

Supplementary Video 3

Step 5. Retractors. (MOV 1738 kb)

Supplementary Video 4

Step 6. Cutting the falciform ligament. (MOV 2023 kb)

Supplementary Video 5

Step 7. Cutting membrane between caudate and left lateral lobes. (MOV 3463 kb)

Supplementary Video 6

Step 8. Placing 1st knot. (MOV 7625 kb)

Supplementary Video 7

Step 9. Tying 1st knot. (MOV 6002 kb)

Supplementary Video 8

Step 10. Resection of 1st lobe. (MOV 10964 kb)

Supplementary Video 9

Step 11. Placing 2nd knot. (MOV 9684 kb)

Supplementary Video 10

Step 12. Tying and resecting 2nd lobe. (MOV 23422 kb)

Supplementary Video 11

Step 13. Closure. (MOV 10275 kb)

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Mitchell, C., Willenbring, H. A reproducible and well-tolerated method for 2/3 partial hepatectomy in mice. Nat Protoc 3, 1167–1170 (2008). https://doi.org/10.1038/nprot.2008.80

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