title: Vitamin K requirement and reproduction in bromadiolone-resistant Norway rats.
abstract: BACKGROUND
  Nucleotide polymorphisms in the VKORC1 gene can be linked to anticoagulant rodenticide resistance in Norway rats (Rattus norvegicus Berkenhout). This provides a fitness advantage to rats exposed to anticoagulant actives, but may also cause fitness costs. The vitamin K requirement and reproductive parameters of bromadiolone-resistant rats (Westphalian resistant strain; VKOR variant Tyr139Cys) and bromadiolone-susceptible Norway rats were compared.
  
  
  RESULTS
  At vitamin K deficiency, blood clotting times increased in all homozygous resistant males within 8 days and in 80% of homozygous resistant females within 15 days. There was little effect on blood clotting in heterozygous males and no effect in heterozygous females and VKOR wild-type individuals. Litter size was about 20% higher in sensitive pairs compared with resistant pairs. Testes growth, male gonad weight, sperm motility and testis cell concentration were unaffected by the mutation.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Julius Kühn-Institute, Federal Research Centre for Cultivated Plants, Institute for Plant Protection in Horticulture and Forestry, Vertebrate Research, Münster, Germany. jens.jacob@jki.bund.de
authors.forename: Jens
authors.initials: J
authors.lastname: Jacob
authors.forename: Stefan
authors.initials: S
authors.lastname: Endepols
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Pelz
authors.forename: Engelbert
authors.initials: E
authors.lastname: Kampling
authors.forename: Trevor G
authors.initials: TG
authors.lastname: Cooper
authors.forename: Ching Hei
authors.initials: CH
authors.lastname: Yeung
authors.forename: Klaus
authors.initials: K
authors.lastname: Redmann
authors.forename: Stefan
authors.initials: S
authors.lastname: Schlatt
mesh_terms: D015110:4-Hydroxycoumarins / Q000494:pharmacology*; D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects; D004351:Drug Resistance; D005260:Female; D005838:Genotype; D008297:Male; D006899:Mixed Function Oxygenases / Q000235:genetics / Q000378:metabolism; D051381:Rats / Q000097:blood / Q000235:genetics / Q000254:growth & development / Q000502:physiology*; D012098:Reproduction / Q000187:drug effects; D012375:Rodent Control; D012378:Rodenticides / Q000494:pharmacology*; D014812:Vitamin K / Q000378:metabolism*; D064417:Vitamin K Epoxide Reductases
chemical_list: D015110:4-Hydroxycoumarins; D012378:Rodenticides; D014812:Vitamin K; D006899:Mixed Function Oxygenases; D064417:Vitamin K Epoxide Reductases; C021636:bromadiolone