Distribution and frequency of VKORC1 sequence variants conferring resistance to anticoagulants in Mus musculus

Pest Manag Sci. 2012 Feb;68(2):254-9. doi: 10.1002/ps.2254. Epub 2011 Sep 6.

Abstract

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.

MeSH terms

  • Amino Acid Substitution
  • Animals
  • Anticoagulants*
  • Azores
  • Drug Resistance / genetics*
  • Gene Frequency
  • Genetic Variation
  • Germany
  • Mice / genetics*
  • Mixed Function Oxygenases / genetics*
  • Rodent Control
  • Switzerland
  • Vitamin K Epoxide Reductases

Substances

  • Anticoagulants
  • Mixed Function Oxygenases
  • VKORC1 protein, human
  • Vitamin K Epoxide Reductases