SCIENTIFIC RepoRts | (2018) 8:4535 | DOI:10.1038/s41598-018-22815-7
VKORC1 sequence variants
associated with resistance to
anticoagulant rodenticides in Irish
populations of Rattus norvegicus
and Mus musculus domesticus
, Mark R. Lynch
, Colin V. Prescott
, Tracy Clegg
, Michael Loughlin
, Colm Moore
& Richard Faulkner
While resistance to anticoagulant rodenticides is known to occur in many European populations
of Norway rat and house mouse, to-date no data is available on the occurrence in Ireland of such
resistance. No genetic evidence for the occurrence of resistance was found in 65 Norway rat samples
analysed, indicative of an absence, or low prevalence, of resistance in rats in at least the Eastern region
of the island of Ireland. The presence of two of the most commonly found amino acid substitutions
Leu128Ser and Tyr139Cys associated with house mouse resistance to anticoagulant rodenticides
was conrmed. The occurrence of two such mutations is indicative of the occurrence of resistance to
anticoagulant rodenticides in house mice in the Eastern region of the island of Ireland.
Following their introduction in the 1950s, warfarin and the structurally similar anticoagulant rodenticides (e.g.
chlorophacinone and coumatetralyl), resulted in radical changes in rodent pest management practice. e newly
introduced rodenticides had delayed action, with the result that mortality followed days or weeks aer initiation
of treatment, an eect that rendered them especially suitable for use to control Norway rats, also known as brown
rats (Rattus norvegicus), a species that displays neophobic reactions. Reecting the higher tolerance of house mice
(Mus musculus) to such compounds, the use of warfarin and other rst generation anticoagulants for their control
was frequently unsatisfactory
Following the identication in 1958 of warfarin resistant rat populations in Scotland
, such resistance was sub-
sequently conrmed at locations in Wales, in England
, in Denmark
, in Germany
, in Belgium
and is now con-
sidered widespread. e rst reports of warfarin-resistant mice populations were published in the early 1960s
As a consequence of increasing concerns generated by the identication of warfarin resistant rodent popula-
tions, industry developed the more potent anticoagulant rodenticides bromadiolone, brodifacoum, difenacoum,
difethialone and ocoumafen, known as second generation anticoagulant rodenticides. As in the case of the
rst-generation compounds, these reect the 4-hydroxycoumarin structure, but display increased lipophilicity
that results in their having longer half-lives
Anticoagulant rodenticides being vitamin K antagonists, block Vitamin K metabolism in the liver by prevent-
ing the enzyme vitamin K epoxide reductase (VKOR) from reducing vitamin K epoxide to vitamin K. Vitamin
K, an essential co-factor for the activation of a number of vitamin K-dependant coagulation factors, plays an
Molecular Virology Laboratory, Department of Agriculture, Food and the Marine Laboratories, Backweston Campus,
Celbridge, Co Kildare, Ireland.
Chairman, Campaign for Responsible Rodenticide Use Ireland CLG, c/o Glendine, 36
Ludford Drive, Dundrum, Dublin 16, Ireland.
School of Animal and Microbial Sciences, The University of Reading,
Whiteknights, Reading, RG6 6AJ, United Kingdom.
Centre for Veterinary Epidemiology and Risk Analysis, School
of Veterinary Medicine, University College Dublin, Beleld, Ireland.
Emel Consulting, Roundwood, Co Wicklow,
Ecolab Ireland, Forest Park, Mullingar Industrial Estate, Mullingar, Co Westmeath, Ireland.
Ltd., Hazel House, Millennium Park, Naas, Co Kildare, Ireland. Correspondence and requests for materials should be
addressed to M.R.L. (email: firstname.lastname@example.org)
Received: 16 October 2017
Accepted: 28 February 2018
Published: xx xx xxxx