Elevated difenacoum metabolism is involved in the difenacoum‐resistant phenotype observed in Berkshire rats homozygous for the L120Q mutation in the vitamin K epoxide reductase complex subunit 1 (Vkorc1) gene. Issue 6 (21st February 2018)

• Record Type: Journal Article
• Authors: Boitet, Maylis; Hammed, Abdessalem; Chatron, Nolan; Debaux, Jean Valéry; Benoit, Etienne; Lattard, Virginie
• Is Part Of: Pest management science. Volume 74:Issue 6(2018)
• Page Start: 1328
• Page End: 1334
• Publication Date: 2018-02-21
• Subjects: Rattus norvegicus -- rodenticide -- difenacoum -- resistance -- vitamin K epoxide reductase -- cytochrome P450; Pests -- Control -- Periodicals; Pesticides -- Periodicals; 632.9
• DOI: 10.1002/ps.4797
• Languages: English
• ISSNs: 1526-498X

Abstract

Abstract: BACKGROUND: Soon after difenacoum began to be used, resistance to this rodenticide was detected in rats in northeast Hampshire and northwest Berkshire in England. Resistance to difenacoum has been reported to be stronger in rats from Berkshire than in rats from Hampshire. Surprisingly, after the discovery of the vitamin K epoxide reductase complex subunit 1 ( Vkorc1 ) gene, rats from Berkshire and Hampshire were all shown to be homozygous for the L120Q mutation in Vkorc1 . RESULTS: This study aimed to evaluate the resistance of Berkshire rats to confirm their extreme resistance and determine mechanisms supporting this resistance. For this purpose, we created a quasicongenic rat F7 strain by using a Berkshire rat as a donor to introduce the L120Q mutation in Vkorc1 into the genetic background of an anticoagulant‐susceptible recipient strain. The use of F7 rats enabled demonstration of (i) the level of resistance to difenacoum conferred by the L120Q mutation, (ii) co‐dominance of the L120 and Q120 alleles, (iii) the extreme resistance of Berkshire rats compared with Q120/Q120 rats as a consequence of additional resistance mechanisms, and (iv) the involvement of cytochrome P 450 (CYP450) enzymes in this extreme resistance. CONCLUSION: This study demonstrated that elevated CYP450 oxidative metabolism leading to accelerated difenacoum detoxification is involved in the Berkshire phenotype. © 2017 Society of Chemical Industry Abstract : This article demonstrates the extraordinary resistance of Berkshire rats to difenacoum and the presence of a metabolic component underlying this hyper‐resistance in addition to the mutation of Vkorc1 gene.