Fig. 1.
F8-deficient thrombosuppression and design of the Leiden ENU mutagenesis screen. (A) The mating scheme and observed distributions of the F5L/+ Tfpi+/− F8 deficiency rescue experiments. F8− results in suppression of the F5L/L Tfpi+/− phenotype. (B) The mating scheme and observed distribution of the Leiden screen. F5L/L Tfpi+/+ male mice were mutagenized with either 1 × 150 mg/kg or 3 × 90 mg/kg ENU and were bred with nonmutagenized F5L/+ Tfpi+/− females. Fifteen and eighty-three F5L/L Tfpi+/− progeny, respectively were observed in each of the dosing regimens, with more than twice the rate of F5L/L Tfpi+/− survivors in the progeny of the 3 × 90 mg/kg-treated mice. (C) There was no significant difference in survival between male and female F5L/L Tfpi+/− putative suppressor mice (P = 0.384). Normal weaning and breeding ages are 20 d and 42 d, respectively. (D) F5L/L Tfpi+/− putative suppressor mice were significantly smaller than their nonF5L/L Tfpi+/− littermates. (E) F5L/L Tfpi+/− putative suppressors were smaller than their littermates of other genotypes (P < 8.8 × 10−12 for B6 and P = 2.2 × 10−16 for mixed B6-129S1) regardless of whether they were on the pure B6 or mixed B6-129S1 genetic backgrounds (P = 0.327 between B6 and mixed backgrounds).