VKORC1 mutations associated with resistance to rodenticides in Mus musculus domesticus in four Italian islands

Human commensal rodents can be extremely harmful to small islands biocenoses. Eradication of invasive rodents is often one of the most direct methods to protect island biodiversity and most of them are carried out using anticoagulant rodenticides (ARs). These compounds act by inhibiting the vitamin K 2,3-epoxide reductase (VKORC) complex of the vitamin K synthesis cycle, an essential cofactor for blood clotting. The phenomenon of resistance to ARs is among the principal reasons for their low efficiency in the management of invasive rodents. Resistance is mainly due to Single Nucleotide Polymorphisms (SNPs) in the vkorc1 gene that confer resistance to ARs. The occurrence and the frequency of this SNPs is poorly known for the population of house mice Mus musculus domesticus on the Mediterranean islands. We analysed the three exons of the vkorc1 gene on four islands of central-southern Italy and we found resistance-related mutations on three of them. Particularly, we found the Tyr139Cys mutation on San Domino Island and Ventotene Island and the Glu155Lys on Pantelleria Island and Ventotene Island. San Nicola Island was the only one showing no resistance-related mutations. Tyr139Cys is one of the most frequent amino acid substitutions occurring in the vkorc1 gene in resistant mice and rats in Europe, and it is known to confer resistance to ARs also in heterozygous condition. Glu155Lys was only detected in Norway rats so far and this is the first record of this mutation in the house mouse. Our results preliminarily suggest a wide distribution of resistance-related mutations in insular Italy and therefore a urgent need for a safer, more conscious use of ARs.