Characterization of bromadiolone resistance in a danish strain of Norway rats, <i>rattus norvegicus</i>, by hepatic gene expression profiling of genes involved in vitamin k‐dependent γ‐carboxylation

Markussen, Mette D K; Heiberg, Ann-Charlotte; Fredholm, Merete; Kristensen, Michael

doi:10.1002/jbt.20201

Cited by 14 publications

(15 citation statements)

References 31 publications

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“…This gene is located on the chromosome 7 in mice and on the chromosome 1 in rats. Single nucleotide polymorphisms of this gene were immediately proposed to be responsible for resistance to AVK (Grandemange et al, 2009; Hodroge, Longin-Sauvageon, Fourel, Benoit, & Lattard, 2011; Pelz et al, 2005;Rost et al, 2004) and appeared to support the resistance process in western Europe, even if cohabitation of target resistance and metabolic resistance had been demonstrated in Denmark (Markussen, Heiberg, Fredholm, & Kristensen, 2007.…”

Section: Introductionmentioning

confidence: 99%

Adaptative evolution of theVkorc1gene inMus musculus domesticusis influenced by the selective pressure of anticoagulant rodenticides

Goulois

Lambert

Legros³

et al. 2017

Ecology and Evolution

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Anticoagulant rodenticides are commonly used to control rodent pests worldwide. They specifically inhibit the vitamin K epoxide reductase (VKORC1), which is an enzyme encoded by the Vkorc1 gene, involved in the recycling of vitamin K. Therefore, they prevent blood clotting. Numerous mutations of Vkorc1 gene were reported in rodents, and some are involved in the resistant to rodenticides phenotype. Two hundred and sixty‐six mice tails were received from 65 different locations in France. Coding sequences of Vkorc1 gene were sequenced in order to detect mutations. Consequences of the observed mutations were evaluated by the use of recombinant VKORC1. More than 70% of mice presented Vkorc1 mutations. Among these mice, 80% were homozygous. Contrary to brown rats for which only one predominant Vkorc1 genotype was found in France, nine missense single mutations and four double mutations were observed in house mice. The single mutations lead to resistance to first‐generation antivitamin K (AVKs) only and are certainly associated with the use of these first‐generation molecules by nonprofessionals for the control of mice populations. The double mutations, probably obtained by genetic recombination, lead to in vitro resistance to all AVKs. They must be regarded as an adaptive evolution to the current use of second‐generation AVKs. The intensive use of first‐generation anticoagulants probably allowed the selection of a high diversity of mutations, which makes possible the genetic recombination and consequently provokes the emergence of the more resistant mutated Vkorc1 described to date.

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Section: Introductionmentioning

confidence: 99%

Adaptative evolution of theVkorc1gene inMus musculus domesticusis influenced by the selective pressure of anticoagulant rodenticides

Goulois

Lambert

Legros³

et al. 2017

Ecology and Evolution

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“…A metabolic resistance due to the increased metabolism of AVKs as suggested in roof rats (Rattus rattus), 4,5 which could also be detected in brown rats (Rattus norvegicus), even in association with the target resistance mechanism. 6,7 The target resistance corresponds to mutations or polymorphisms (SNPs) in the Vkorc1 gene resulting in a decrease in the inhibitory effect of AVKs towards the VKOR activity catalysed by the VKORC1 enzyme. Numerous mutations or SNPs have been detected in this gene that are associated with resistant phenotype in rats, 8 -10 mice 8,9 and humans.…”

Section: Introductionmentioning

confidence: 99%

Study of the efficiency of anticoagulant rodenticides to controlMus musculus domesticusintrogressed withMus spretus Vkorc1

Goulois

Hascoët²,

Dorani

et al. 2016

Pest. Manag. Sci.

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“…If this VKORC1 mutationinduced mechanism can be excluded in the case of the natural resistance to VKA of females, differences in the expression level of genes encoding putative partner proteins of VKORC1, such as calumenin (Wallin et al, 2001), epoxide hydrolase (Guenthner et al, 1998) or glutathione transferase (Cain et al, 1998), could modify this VKOR activity. Other mechanisms could be suspected to explain the better tolerance of females to VKA, such the existence of metabolic differences between males and females (Huber et al, 1999;Markussen et al, 2007Markussen et al, , 2008Mugford and Kedderis, 1998;Waxman, 1988), or even a natural resistance of the coagulation cascade (Lemini et al, 2007) after VKA administration.…”

Section: Introductionmentioning

confidence: 99%

Origin of the gender differences of the natural resistance to antivitamin K anticoagulants in rats

et al. 2016

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Vitamin K antagonists (VKA) are used either in human medicine to prevent thromboembolic disorders or as rodenticides for pest control management. In rodents, female rats are described to be more tolerant to the action of vitamin K antagonists than males. Nevertheless, the mechanism of this greatest tolerance is still unknown and this study aims to identify the origin of this greatest tolerance after VKA administration. Therefore, difethialone, one of the most powerful VKA was used in this study. A possible difference in the pharmacokinetics of difethialone between males and females was first investigated. The determination of the pharmacokinetic parameters allowed to exclude a pharmacokinetic origin of the greatest tolerance of females to VKA. Thus, a natural resistance to difethialone of the liver VKOR activity, which is the target of VKA, was thus explored in females. The determination of Ki towards difethialone in liver microsomes allowed to also exclude this hypothesis. Therefore, equipment in vitamin K-dependent clotting factors and properties of vitamin K-dependent clotting factors were explored. Basal activity of clotting factors VII and X were found significantly higher in females of respectively 43% and 21%. Moreover, after VKA administration, half-lives of clotting factors II and X were found significantly longer in females of respectively 27% and 10% and a lag time of 4h before the beginning of the decay of factor VII was observed only in females after difethialone administration. The greater tolerance of female rats to VKA is thus due a stronger basal pool of vitamin K-dependent clotting factors VII and X and to a slower decline of vitamin K-dependent clotting factors II, VII and X after VKA administration.

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Characterization of bromadiolone resistance in a danish strain of Norway rats, rattus norvegicus, by hepatic gene expression profiling of genes involved in vitamin k‐dependent γ‐carboxylation

Cited by 14 publications

References 31 publications

Adaptative evolution of theVkorc1gene inMus musculus domesticusis influenced by the selective pressure of anticoagulant rodenticides

Adaptative evolution of theVkorc1gene inMus musculus domesticusis influenced by the selective pressure of anticoagulant rodenticides

Study of the efficiency of anticoagulant rodenticides to controlMus musculus domesticusintrogressed withMus spretus Vkorc1

Origin of the gender differences of the natural resistance to antivitamin K anticoagulants in rats

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