Abcb5-deficient mice show a subtle, pleiotropic phenotype indicating a role for this transporter in intermediary metabolism
ABCB5 is a member of the ATP-binding cassette transporter superfamily that is expressed as a full transporter (ABCB5FL) and half transporter (ABCB5β). The ABCB5FL transporter mediates low-level multidrug resistance in cancer and is normally expressed in the prostate and testis, while ABCB5β has been found to be a marker of melanoma and limbal stem cells and is expressed in pigmented cells. To explore ABCB5's role in normal physiology, we generated Abcb5-deficient C57BL/6J mice by the deletion of Abcb5 exon 2, knocking out both forms of ABCB5, which were completely phenotyped. The mice were fertile and demonstrated altered bioenergetics and fat metabolism, along with alterations in their blood composition, including anisocytosis and decreased white blood cells and platelet counts. This study uncovers further avenues of investigation into the role of Abcb5 in intermediary metabolism, particularly in relation to atherogenesis.
Authors
- Jan Rozman (ORCID: https://orcid.org/0000-0002-8035-8904)
- Di Xia (ORCID: https://orcid.org/0000-0002-2748-0679)
- Martin Hrabě de Angelis (ORCID: https://orcid.org/0000-0002-7898-2353)
- Helmut Fuchs (ORCID: https://orcid.org/0000-0002-5143-2677)
- Birgit Rathkolb (ORCID: https://orcid.org/0000-0003-1239-0547)
- Lino Tessarollo (ORCID: https://orcid.org/0000-0001-6420-772X)
- Marie Fourrez
- Marion Horsch
- Cornelia Prehn (ORCID: https://orcid.org/0000-0002-1274-4715)
- Juan Antonio Aguilar‐Pimentel (ORCID: https://orcid.org/0000-0002-4694-7107)
- Michael M. Gottesman (ORCID: https://orcid.org/0000-0001-8908-2097)
- Florence Rodriguez Gaudray
- Tanja Klein‐Rodewald (ORCID: https://orcid.org/0000-0002-9121-106X)
- Louise Gerard
- Jean‐Pierre Gillet (ORCID: https://orcid.org/0000-0003-2453-590X)
- Valérie Gailus‐Durner (ORCID: https://orcid.org/0000-0002-6076-0111)
- Lore Becker (ORCID: https://orcid.org/0000-0002-6890-4984)
- Nadine Spielmann (ORCID: https://orcid.org/0000-0003-2699-0068)
- Benoît Bihin (ORCID: https://orcid.org/0000-0002-8713-6319)
- Eileen Southon
- Wilfred D. Vieira
- Johannes Beckers (ORCID: https://orcid.org/0000-0001-7874-3822)
Institutions
- University of Namur (BE)
- Helmholtz Zentrum München (DE)
- CHU Dinant Godinne UCL Namur (BE)
- Cancer Research Center (US)
- Frederick National Laboratory for Cancer Research (US)
- Czech Academy of Sciences, Institute of Molecular Genetics (CZ)
- National Cancer Institute (US)
- Center for Cancer Research (US)
- Deutsches Diabetes-Zentrum e.V. (DE)
- German Center for Diabetes Research (DE)
- Heinrich Heine University Düsseldorf (DE)
- Technical University of Munich (DE)
- Ludwig-Maximilians-Universität München (DE)
Publication Details
- Journal
- iScience
- Published
- 2025-09-23
- DOI
- https://doi.org/10.1016/j.isci.2025.113617
- Primary Topic
- Amino Acid Enzymes and Metabolism
- Type
- article
- Field-Weighted Citation Impact
- 0.00