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Distribution and frequency of VKORC1 sequence variants conferring resistance to anticoagulants in Mus musculus
Hans-Joachim Pelz1, Simone Rost, Elisabeth Müller
1Julius Kühn-Institut, Federal Research Centre for Cultivated Plants, Vertebrate Research, Münster, Germany. hans-joachim.pelz@jki.bund.de
Background:
Emerging resistance to anticoagulant rodenticides may significantly impair house mouse (Mus musculus L.) control. As in humans and rats, sequence variants in the gene vitamin K epoxide reductase complex subunit 1 (VKORC1) of house mice are strongly implicated in the responses of mice to anticoagulants. This study gives a first overview of the distribution and frequency of such potentially resistance-conferring sequence variants in house mice, based on tissue samples from 30 populations in Germany, Switzerland and the Azores.
Results:
Except for one population from south Germany, sequence variants were found in individuals from all locations sampled (29 out of 30 sites surveyed), with less than 10% of the individuals matching the wild-type genotype. The most frequent and widespread amino acid substitutions were Leu128Ser, Tyr139Cys and a group of linked sequence changes (Arg12Trp/Ala26Ser/Ala48Thr/Arg61Leu). Where these substitutions occurred as the sole variant, the proportion of homozygous individuals was 72-83%.
Conclusions:
An evaluation of published data revealed that the three most frequently found sequence variants are associated with a substantial loss of rodenticide efficacy of first-generation anticoagulants (e.g. warfarin, coumatetralyl), as well as the second-generation compound bromadiolone and most probably also difenacoum. Knowledge of the distribution and frequency of resistance-conferring sequence variants will stimulate their further functional characterisation and facilitate the choice of effective active substances for house mouse control.
Insights
House mouse populations across Germany, Switzerland, and the Azores show widespread resistance to rodenticides due to VKORC1 gene variants. These genetic changes significantly reduce the effectiveness of common anticoagulant treatments.
Area of Science:
- Pest Management
- Genetics
- Molecular Biology
Background:
- Emerging resistance to anticoagulant rodenticides threatens effective house mouse control.
- Sequence variants in the vitamin K epoxide reductase complex subunit 1 (VKORC1) gene are linked to anticoagulant resistance in house mice, similar to humans and rats.
- This study investigates the distribution and frequency of VKORC1 variants in German, Swiss, and Azorean house mouse populations.
Purpose of the Study:
- To provide the first overview of the distribution and frequency of VKORC1 sequence variants in house mice.
- To identify specific VKORC1 variants associated with resistance to anticoagulant rodenticides.
- To inform strategies for effective house mouse control.
Main Methods:
- Analysis of tissue samples from 30 house mouse populations across Germany, Switzerland, and the Azores.
- Sequencing of the VKORC1 gene to identify variants.
- Genotyping to determine the frequency of wild-type and variant alleles.
Main Results:
- VKORC1 sequence variants were found in 29 out of 30 surveyed populations, with less than 10% of individuals exhibiting the wild-type genotype.
- The most common amino acid substitutions identified were Leu128Ser, Tyr139Cys, and a linked group of changes (Arg12Trp/Ala26Ser/Ala48Thr/Arg61Leu).
- Homozygous individuals for these sole variants ranged from 72-83%.
Conclusions:
- The identified VKORC1 variants significantly reduce the efficacy of first-generation (e.g., warfarin) and second-generation (e.g., bromadiolone, difenacoum) anticoagulants.
- Understanding the prevalence of these resistance-conferring variants is crucial for selecting effective rodenticides.
- Further functional characterization of these variants will aid in developing targeted pest control strategies.
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