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ATP-binding cassette (ABC) transporters are of major importance for the restricted access of toxins and drugs to the human body. At the body's barrier tissues like the blood-brain barrier, these transporters are highly represented. Especially, ABCB1 (P-glycoprotein) has been a priority target of pharmaceutical research, for instance, to aid chemotherapy of cancers, therapy resistant epilepsy, and lately even neurodegenerative diseases. To improve translational research, the humanization of mouse genes has become a popular tool although, like recently seen for Abcb1, not all approaches were successful. Here, we report the characterization of another unsuccessful commercially available ABCB1 humanized mouse strain. In vivo assessment of transporter activity using positron emission tomography imaging revealed a severe reduction of ABCB1 function in the brain of these mice. Analyses of brain mRNA and protein expression showed that the murine Abcb1a gene is still expressed in homozygous humanized animals while expression of the human gene is minimal. Promoter region analyses underpinned that the introduced human gene might dysregulate normal expression and provided insights into the regulation of both transcription and translation of Abcb1a. We conclude that insertion of the human coding DNA sequence (CDS) into exon 3 instead of exon 2 most probably represents a more promising strategy for Abcb1a humanization.
Pubmed ID: 30345087
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Software tool as Windows client application for targeted proteomics method creation and quantitative data analysis. Open source document editor for creating and analyzing targeted proteomics experiments. Used for large scale quantitative mass spectrometry studies in life sciences.
View all literature mentionsSoftware application with data analysis tools and spreadsheet templates to track and visualize data. It is used to manage and process data.
View all literature mentionsConsortium to build comprehensive parts list of functional elements in human genome. This includes elements that act at protein and RNA levels, and regulatory elements that control cells and circumstances in which gene is active. Data from 2012-present.
View all literature mentionsMus musculus with name B6.C-Tg(CMV-cre)1Cgn/J from IMSR.
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
View all literature mentionslaboratory mouse with name C57BL/6N from MGI.
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