Seasonal diet-based resistance to anticoagulant rodenticides in the fossorial water vole (Arvicola amphibius)

Rami Abil Khalil (1) , Brigitte Barbier (1) , Ambre Fafournoux (1) , Ali Barka Mahamat (1) , Aurélie Marquez (1) , Kevin Poissenot (2) , Matthieu Keller (2) , Amélie Desvars-Larrive (3, 4) , Javier Fernandez-De-Simon (5) , Michael Coeurdassier (5) , Etienne Benoit (1) , Sébastien Lefebvre (6, 1) , Adrien Pinot (1) , Virginie Lattard (1)

1 RS2GP - Rongeurs Sauvages, Risques Sanitaires et Gestion des Populations - UR 1233
2 PRC - Physiologie de la reproduction et des comportements [Nouzilly]
3 Vetmeduni - University of Veterinary Medicine [Vienna]
4 CSHV - Complexity Science Hub Vienna
5 LCE - Laboratoire Chrono-environnement (UMR 6249)
6 SNBA-VAS - Service de nutrition et de bromatologie animale

Anticoagulant rodenticides (AR) resistance has been defined as "a major loss of efficacy due to the presence of a strain of rodent with a heritable and commensurately reduced sensitivity to the anticoagulant". The mechanism that supports this resistance has been identified as based on mutations in the Vkorc1 gene leading to severe resistance in rats and mice. This study evaluates the validity of this definition in the fossorial water vole and explores the possibility of a non-genetic diet-based resistance in a strict herbivorous rodent species. Genetic support was explored by sequencing the Vkorc1 gene and the diet-based resistance was explored by the dosing of vitamins K in liver of voles according to seasons. From a sample of 300 voles, only 2 coding mutations, G71R and S149I, were detected in the Vkorc1 gene in the heterozygous state with low allele frequencies (0.5-1%). These mutations did not modify the sensitivity to AR, suggesting an absence of genetic Vkorc1-based resistance in the water vole. On the contrary, vitamin K1 was shown to be 5 times more abundant in the liver of the water vole compared to rats. This liver concentration was shown to seasonally vary, with a trough in late winter and a peak in late spring/early summer related to the growth profile of grass. This increase in concentration might be responsible for the increased resistance of water voles to AR. This study highlights a non-genetic, diet-related resistance mechanism in rodents to AR. This diet-based resistance might explain the different evolution of the Vkorc1 gene in the fossorial water vole compared to rats and mice.

Mots clés: Water vole; Anticoagulant rodenticides; VKORC1; Vitamin K; Diet-based resistance

Domaines: Toxicologie et chaîne alimentaire; Ecotoxicologie; Biochimie [q-bio.BM]; Médecine vétérinaire et santé animale; Alimentation et Nutrition

Rami Abil Khalil, Brigitte Barbier, Ambre Fafournoux, Ali Barka Mahamat, Aurélie Marquez, et al.. Seasonal diet-based resistance to anticoagulant rodenticides in the fossorial water vole (Arvicola amphibius). Environmental Research, 2021, 200, ⟨10.1016/j.envres.2021.111422⟩. ⟨hal-03257639v2⟩