The mitochondrial uncoupling protein 2 gene is causal for the spontaneous polycystic liver diseases in mice

Misa Hirose; Paul Schilf; Sarah Rohde; Yask Gupta; Tiphaine Sancerni; Marie-Clotilde Alves-Guerra; Christian Sina; Robert Jaster; Bruno Miroux; Saleh M Ibrahim

doi:10.1016/j.mito.2017.10.011

The mitochondrial uncoupling protein 2 gene is causal for the spontaneous polycystic liver diseases in mice

Mitochondrion. 2018 Sep:42:50-53. doi: 10.1016/j.mito.2017.10.011. Epub 2017 Nov 14.

Authors

Affiliations

¹ Lübeck Institute of Experimental Dermatology, University of Lübeck, Germany.
² Division of Gastroenterology, Department of Medicine II, University Medicine Rostock, Rostock, Germany.
³ Inserm, U1016, Institut Cochin; Paris Cedex 75014, France; CNRS UMR 8104, Paris Cedex, 75014, France; Université Paris Diderot, Paris Cedex 75014, France.
⁴ Inserm, U1016, Institut Cochin; Paris Cedex 75014, France; CNRS UMR 8104, Paris Cedex, 75014, France; Université Paris Descartes UMRS1016, Paris Cedex 75014, France.
⁵ Institute for Nutritional Medicine, University of Lübeck, Lübeck, Germany.
⁶ Institute of Physical and Chemical Biology, UMR 7099, CNRS, University Paris-Diderot, Sorbonne Paris Cités, Paris, France.
⁷ Lübeck Institute of Experimental Dermatology, University of Lübeck, Germany; College of Medicine, Sharjah Institute for Medical Research, University of Sharjah, AE-27272, United Arab Emirates. Electronic address: Saleh.Ibrahim@uksh.de.

PMID: 29154852
DOI: 10.1016/j.mito.2017.10.011

Abstract

Polycystic liver diseases (PCLDs) are autosomal dominant disorders. To date, 3 genes are known to be associated with the disease, SEC63 and PRKCSH and LRP5. Here, we report that mice deficient in the mitochondrial uncoupling protein 2 gene (Ucp2^-/-) spontaneously developed PCLDs when they were over 12months old. Macroscopical observation, blood chemistry as well as histopathological analysis demonstrated the PCLDs found in Ucp2^-/- mice were very similar to the findings in human PCLDs. This is the first report describing the gene encoding mitochondrial protein is causative for PCLDs. UCP2 may be a biomarker of the PCLDs in humans.

Keywords: Mitochondria; Mouse model; Polycystic liver disease (PCLD); Uncoupling protein 2 (UCP2).

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Blood Chemical Analysis
Cysts / genetics*
Disease Models, Animal
Female
Histocytochemistry
Liver / pathology
Liver Diseases / genetics*
Male
Mice, Inbred C57BL
Uncoupling Protein 2 / deficiency*

Substances

Uncoupling Protein 2

Supplementary concepts

Polycystic liver disease