Generation and characterization of an ABCC1 humanized mouse model (HABCC1FLX/FLX) with knockout capability

Markus Krohn, Viktoria Zoufal, Severin Mairinger, Thomas Wanek, Kristin Paarmann, Thomas Brüning, Ivan Eiriz, Mirjam Brackhan, Oliver Langer, Jens Pahnke*

*Corresponding author for this work
1 Citation (Scopus)


ATP-binding cassette (ABC) transporters such as ABCB1 (P-glycoprotein), ABCC1 (MRP1), and ABCG2 (BCRP) are well known for their role in rendering cancer cells resistant to chemotherapy. Additionally, recent research provided evidence that, along with other ABC transporters (ABCA1 and ABCA7), they might be cornerstones to tackle neurodegenerative diseases. Overcoming chemoresistance in cancer, understanding drug-drug interactions, and developing efficient and specific drugs that alter ABC transporter function are hindered by a lack of in vivo research models, which are fully predictive for humans. Hence, the humanization of ABC transporters in mice has become a major focus in pharmaceutical and neurodegenerative research. Here, we present a characterization of the first Abcc1 humanized mouse line. To preserve endogenous expression profiles, we chose to generate a knockin mouse model that leads to the expression of a chimeric protein that is fully human except for one amino acid. We found robust mRNA and protein expression within all major organs analyzed (brain, lung, spleen, and kidney). Furthermore, we demonstrate the functionality of the expressed human ABCC1 protein in brain and lungs using functional positron emission tomography imaging in vivo. Through the introduction of loxP sites, we additionally enabled this humanized mouse model for highly sophisticated studies involving cell type-specific transporter ablation. Based on our data, the presented mouse model appears to be a promising tool for the investigation of cell-specific ABCC1 function. It can provide a new basis for better translation of preclinical research.

Original languageEnglish
JournalMolecular pharmacology
Issue number2
Pages (from-to)138-147
Number of pages10
Publication statusPublished - 2019

Research Areas and Centers

  • Academic Focus: Center for Infection and Inflammation Research (ZIEL)


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