1 Department of Integrated Pest Management, Faculty of Agricultural Sciences, Aarhus University, Aarhus University2 Danish Pest Infestation Laboratory, Faculty of Agricultural Sciences, Aarhus University, Aarhus University3 Department of Agroecology - Danish Pest Infestation Laboratory, Department of Agroecology, Science and Technology, Aarhus University4 University of Copenhagen, Faculty of Life Sciences5 Department of Agroecology - Entomology and Plant Pathology, Department of Agroecology, Science and Technology, Aarhus University6 Department of Agroecology - Entomology and Plant Pathology, Department of Agroecology, Science and Technology, Aarhus University
Anticoagulant resistance in Norway rats (Rattus norvegicus) has been associated with two genes, VKORC1 and Calumenin, which encodes proteins essential to the vitamin K-dependent gamma-carboxylation system. Mutations in the VKORC1 gene are considered the genetic basis for anticoagulant resistance in European strains of Norway rats while high hepatic levels of calumenin has been suggested responsible for resistance in an US strain of rats. To characterize the resistance mechanism in a Danish strain of bromadiolone-resistant Norway rats (with an Y139C-VKORC1 mutation), we compared VKORC1 and Calumenin liver gene expression between resistant and anticoagulant-susceptible rats upon saline and bromadiolone-administration. The resistant male and female rats had significantly lower constitutive VKORC1 expression (57 % and 63 %) compared to the susceptible rats (100 %) while the constitutive Calumenin expression was at similar levels in resistant and susceptible rats. Upon bromadiolone exposure, both VKORC1 and Calumenin gene expression was approximately two-fold lower in the resistant male and female rats (51-57 %) compared to the susceptible rats (100%). The low VKORC1 expression may explain the basal lowered VKOR activity and the elevated requirement for vitamin K previously described for Danish resistant rats whereas the low Calumenin expression could be an adaptation to secure a high efficacy of the vitamin K-dependent gamma-carboxylation system during anticoagulant exposure. Our findings for the Danish bromadiolone-resistant strain suggest that genetic anticoagulant resistance in European strains of Norway rats differs markedly from the genetic form of resistance described for an US rat strain.