Mutations in the VKORC1 Gene of Wild Rats and Mice
Author Information
Author(s): Simone Rost, Hans-Joachim Pelz, Sandra Menzel, Alan D MacNicoll, Vanina León, Ki-Joon Song, Thomas Jäkel, Johannes Oldenburg, Clemens R Müller
Primary Institution: Department of Human Genetics, University of Wuerzburg, Wuerzburg, Germany
Hypothesis
Are novel mutations in the VKORC1 gene a response to 50 years of selection pressure by warfarin?
Conclusion
The study confirms that the VKORC1 gene is the main target for mutations that confer warfarin resistance in wild rats and mice.
Supporting Evidence
- The study identified 18 novel and five published missense mutations in the VKORC1 gene.
- Mutations were found in rats and mice from Europe, South Africa, East Asia, and both North and South America.
- Most mutations reduced VKOR activity compared to the wild-type protein.
Takeaway
Scientists found new changes in a gene that helps rats and mice resist a poison called warfarin, which has been used for a long time to control pests.
Methodology
The VKORC1 genes of over 250 rats and mice were sequenced, and mutations were analyzed through recombinant expression in a human cell line.
Limitations
The in vitro enzyme assay used may not convincingly demonstrate warfarin resistance for all mutant proteins.
Participant Demographics
Rats and mice from anticoagulant-exposed areas across four continents.
Digital Object Identifier (DOI)
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