Abstract/Summary

Anticoagulant resistance was discovered in UK House mice almost 60 years ago, soon after the introduction of the first-generation anticoagulant rodenticides (FGARs). Resistant individuals were found to survive field strength anticoagulant baits, and in response, more potent second generation anticoagulant rodenticides (SGARs) were developed. Practical resistance to some SGARs is now raising major concerns. This thesis focuses on the development and implementation of methodologies to investigate resistance in mice.  Susceptibility baseline data were produced for four FGARs using albino susceptible House mice.  Resistance baselines were produced using House mice homozygous for the VKORC1 mutation Y139C, against four FGARs and against five SGARs.  Resistance baselines were produced using House mice heterozygous for the VKORC1 mutation Y139C against five SGARs. For homozygous resistant mice, resistance factors (RFs) were estimated for four FGARs and five SGARs; and for the SGAR bromadiolone and all four FGARs, the magnitude of the RF was sufficient to suggest practical resistance (with a high likelihood of treatment failure). For heterozygous resistant mice, only the SGAR bromadiolone had an RF that would suggest some degree of practical resistance, with all other SGARs expected to be efficacious. ii From the above, the continued use of ineffective anticoagulants would be expected to actively select for anticoagulant resistance, and thus exacerbate the control problem. In the UK, resistant populations of House mice carrying the VKORC1 mutations Y139C and L128S are widespread in animals sampled to date, and the high incidence of homozygous resistance would suggest over reliance on ineffective anticoagulants as a major cause. Data presented here is now available globally, online via the RRAC website, where it can be used to make decisions on rodenticide selection for mouse populations that carry the Y139 mutation, and to quantify the magnitude of FGAR resistance against other VKORC1 mutations.