The coagulability of the plasma of blood taken from the retro-orbital sinus of untreated and warfarin-treated wild house mice (Mus musculus L.) was determined. Individual differences were observed in the resting clotting times of animals drawn from three different sources, so-called ‘normal’ (N) mice, home-bred warfarin resistant (HBR) mice and field-caught suspected warfarin resistant (FR) mice. Mice from the three sources also showed wide individual variation in response to injected doses of 1, 5 and 50 mg. of warfarin/kg, body weight. The overall response shown by HBR and FR mice, particularly females, was less than that shown by N animals. Some FR females failed to respond to a dose of 100 mg. of warfarin/kg, body weight.
Normal mice showed a similar response to two identical doses of warfarin (1, 5 or 50 mg./kg. body weight) given at an interval of 3 weeks. They developed a tolerance to repeated daily injected doses of 1 mg. of warfarin/kg, body weight but not to the higher doses (5 and 50 mg./kg.) to which some HBR animals became tolerant.
In comparative 21-day feeding tests with 0·025% warfarin in medium oatmeal, the mortality in N, HBR and FR mice was 100% (27), 64·5% (40/62) and 22·7% (10/44) respectively. Whereas the plasma of all N mice was rendered uncoagulable after 3 days and the animals died within 12 days, the clotting times of the surviving HBR and FR mice (24/59 males and 32/47 females) either were not at any stage appreciably increased or had declined to near normal values by the end of the test period.
In similar tests with 0·025% warfarin in oatmeal bait containing 5% mineral oil, it was found that the clotting ability of the plasma of N, HBR and FR mice was impaired earlier and that mortality in HBR and FR animals was significantly higher (62/67, 92·5% and 7/8, 87·5% respectively).
Three of seven HBR mice died after prolonged feeding on various warfarin baits but only after 186, 197 and 209 days respectively. The inclusion of mineral oil in bait containing 0-0·25% warfarin was more effective in decreasing the coagulability of the blood of these mice than either increasing the concentration of warfarin (to 0·1 and 0·2%) or including sulphaquinoxaline or corn oil.
Studies on mice given warfarin by injection and in feed indicated that in females the level of resistance to warfarin may be assessed on the basis of their response to a single injected dose of warfarin.