title: Study of the efficiency of anticoagulant rodenticides to control Mus musculus domesticus introgressed with Mus spretus Vkorc1.
abstract: BACKGROUND
  Antivitamin K anticoagulant (AVK) rodenticides are commonly used to control rodent pests worldwide. They specifically inhibit the VKORC1 enzyme essential for the recycling of vitamin K, and thus prevent blood clotting and cause death by haemorrhage. Numerous mutations or polymorphisms of the Vkorc1 gene were reported in rodents, and some led to resistance to rodenticides. In house mice (Mus musculus domesticus), adaptive introgression of the Vkorc1 gene from the Algerian mouse (Mus spretus) was reported. This adaptive introgression causes the substitution of four amino acids in M. musculus domesticus.
  
  
  RESULTS
  The consequences of introgression were assessed by (i) the characterisation of the in vivo resistant phenotype of adaptive Vkorc1spr-introgressed mice, (ii) the characterisation of the ex vivo resistance phenotype of the liver VKOR activity and (iii) the comparison of these results with the properties of recombinant VKORC1sprprotein expressed in yeast. The resistance factor (from 1 to 120) induced by the four introgressed polymorphisms obtained using these three approaches was dependent on the AVKs used but were highly correlated among the three approaches.
  
  
  CONCLUSIONS
  The four introgressed polymorphisms were clearly the cause of the strong resistant phenotype observed in the field. In the context of strong selection pressure due to the extensive use of AVKs, this resistant phenotype may explain the widespread distribution of this genotype from Spain to Germany. © 2016 Society of Chemical Industry.
authors.affiliation: USC 1233 INRA-VetAgro Sup, Veterinary School of Lyon, Marcy l'Etoile, France.|Liphatech, Bonnel, Pont du Casse, France.
authors.forename: Joffrey
authors.initials: J
authors.lastname: Goulois
authors.affiliation: Liphatech, Bonnel, Pont du Casse, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Hascoët
authors.affiliation: USC 1233 INRA-VetAgro Sup, Veterinary School of Lyon, Marcy l'Etoile, France.
authors.forename: Khedidja
authors.initials: K
authors.lastname: Dorani
authors.affiliation: USC 1233 INRA-VetAgro Sup, Veterinary School of Lyon, Marcy l'Etoile, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Besse
authors.affiliation: Liphatech, Bonnel, Pont du Casse, France.
authors.forename: Lionel
authors.initials: L
authors.lastname: Legros
authors.affiliation: USC 1233 INRA-VetAgro Sup, Veterinary School of Lyon, Marcy l'Etoile, France.
authors.forename: Etienne
authors.initials: E
authors.lastname: Benoit
authors.affiliation: USC 1233 INRA-VetAgro Sup, Veterinary School of Lyon, Marcy l'Etoile, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Lattard
mesh_terms: D000818:Animals; D000925:Anticoagulants; D005260:Female; D005838:Genotype; D006824:Hybridization, Genetic; D008099:Liver / Q000201:enzymology; D008297:Male; D051379:Mice / Q000235:genetics*; D010641:Phenotype; D010843:Pichia; D011110:Polymorphism, Genetic; D012375:Rodent Control / Q000379:methods*; D012378:Rodenticides; D064417:Vitamin K Epoxide Reductases / Q000235:genetics*
chemical_list: D000925:Anticoagulants; D012378:Rodenticides; D064417:Vitamin K Epoxide Reductases
keywords: Mus musculus domesticus; Mus spretus; VKORC1; antivitamin K; mutation; resistance