title: Distribution and frequency of VKORC1 sequence variants conferring resistance to anticoagulants in Mus musculus.
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.
authors: Julius Kühn-Institut, Federal Research Centre for Cultivated Plants, Vertebrate Research, Münster, Germany. hans-joachim.pelz@jki.bund.de
authors: Hans-Joachim
authors: HJ
authors: Pelz
authors: Simone
authors: S
authors: Rost
authors: Elisabeth
authors: E
authors: Müller
authors: Alexandra
authors: A
authors: Esther
authors: Rainer G
authors: RG
authors: Ulrich
authors: Clemens R
authors: CR
authors: Müller
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D000925:Anticoagulants; D001394:Azores; D004351:Drug Resistance / Q000235:genetics*; D005787:Gene Frequency; D014644:Genetic Variation; D005858:Germany; D051379:Mice / Q000235:genetics*; D006899:Mixed Function Oxygenases / Q000235:genetics*; D012375:Rodent Control; D013557:Switzerland; D064417:Vitamin K Epoxide Reductases
chemical_list: D000925:Anticoagulants; D006899:Mixed Function Oxygenases; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases