Julius Kühn-Institut, Federal Research Centre for Cultivated Plants, Vertebrate Research, Münster, Germany.
Pest Manag Sci. 2012 Feb;68(2):254-9. doi: 10.1002/ps.2254. Epub 2011 Sep 6.
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.
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%.
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.
抗凝血灭鼠剂的新兴抗性可能会严重影响家鼠（Mus musculus L.）的控制。与人类和大鼠一样，家鼠基因维生素 K 环氧化物还原酶复合物亚基 1（VKORC1）中的序列变异强烈暗示了老鼠对抗凝剂的反应。本研究基于来自德国、瑞士和亚速尔群岛的 30 个种群的组织样本，首次概述了这种潜在的抗性赋予序列变异在家鼠中的分布和频率。
除了德国南部的一个种群外，在所调查的 30 个地点中的 29 个地点的个体中都发现了序列变异，不到 10%的个体与野生型基因型匹配。最常见和广泛的氨基酸取代是 Leu128Ser、Tyr139Cys 和一组连锁的序列变化（Arg12Trp/Ala26Ser/Ala48Thr/Arg61Leu）。当这些取代仅作为唯一的变异发生时，纯合个体的比例为 72-83%。
对已发表数据的评估表明，这三种最常发现的序列变异与第一代抗凝剂（如华法林、氯鼠酮）以及第二代化合物溴敌隆的灭鼠效果显著降低有关，而且很可能也与敌鼠灵有关。抗性赋予序列变异的分布和频率的知识将刺激它们的进一步功能特征描述，并有助于选择控制家鼠的有效活性物质。
