Vitamin K requirement and reproduction in bromadiolone‐resistant Norway rats

Abstract

The VKOR variant Tyr139Cys causes considerable physiological cost in Norway rats in terms of vitamin K requirement and reproduction. This may affect the distribution and spread of resistant individuals in the wild. Decreased litter size of resistant parents seems to be due to lowered female reproductive performance, as there was no significant effect of the mutation on any aspects of male reproduction considered, but this requires further study.

New insights into the catalytic mechanism of vitamin K epoxide reductase (VKORC1) – The catalytic properties of the major mutations of rVKORC1 explain the biological cost associated to mutations

“…7 ). It is thus conceivable that a decrease in the VKOR catalytic efficiency (as observed for L120Q, Y139C/F/C) associated or not with an elevated 3‐OH‐vit K production (as observed for mutations in position 139) might cause an increase in dietary requirements of vit K. Indeed, severe increase in dietary requirements was described in resistant rats from Denmark and Germany (i.e., certainly homozygous for Y139C) [16,19] and from Wales (i.e., certainly homozygous for Y139S) [26]. On the contrary, vit K requirements in resistant rats from Scotland (i.e., homozygous for L128Q) [27] are described to be similar to vit K requirements of susceptible rats.…”

“…All these observations are totally in agreement with the catalytic results obtained in this study. Furthermore, in rat homozygous for Y139C, retarded growth [16,17] and cardiovascular calcifications [19] were reported. Both are to be considered as the consequence of a deficiency in vit K. Indeed, Matrix Gla protein (MGP), a VKDP which is considered as an inhibitor of the tissue calcification, is effective under its gamma-carboxylated form only [28,29].…”

“…Moreover, various fitness trade-offs associated with AVKs resistance were described in rats. In some resistant rats, retarded growth [16,17], modification of the reproductive capacities [18,19] vascular calcification [20] were observed associated to the resistance to AVKs. The objective of this work was to study the involvement of the different mutations of Vkorc1 in the biological cost specifically described in various strains of wild rats resistant to AVKs.…”

Increased diphacinone and chlorophacinone metabolism in previously exposed wild caught voles, Microtus californicus

“…Body weight measurements were included in the current study due to the findings of Smith et al that in offspring of wild-caught warfarin resistant rats weight conveyed social dominance (Smith et al, 1994). Differences in the weight of bromadiolone-resistant Norway rats have been shown to effect reproductive success and therefore the spread of resistance (Jacob et al, 2012). Exploiting this "selective disadvantage" has been cited as one way to manage anticoagulant resistance (Greaves, 1986).…”

Peer Review #2 of "Large-scale structure of brown rat (Rattus norvegicus) populations in England: effects on rodenticide resistance (v0.1)"

“…It has been reported that because of pleiotropic costs (on vitamin K requirements, reduced fecundity and growth rate) that anticoagulant resistant rats (from some regions) are at a selective disadvantage in the absence of anticoagulant use compared to susceptible individuals (Jacob et al 2012;Smith et al 1991). Intuitively therefore, these susceptible rats should out-compete their resistant counterparts in the absence of exposure to anticoagulant rodenticides, and it follows that resistance-management strategies should, where possible, include the use of non-anticoagulant rodenticides and non-rodenticide approaches in order to remove selection pressure, and to remove resistant individuals (Buckle 2013;Greaves 1995;Lambert et al 2008;Quy et al 1995;Smith & Greaves 1987).…”