Severe spontaneous bleeding occurs in Dahl-FVIII^−/−rats. Affected animals were closely monitored, and bleeding episodes were recorded. (A) Representative images of spontaneous bleeding in our inbred Dahl-FVIII^−/− rats. (B) Spontaneous bleeding events in homozygous (FVIII^−/−) and heterozygous (FVIII^+/−) Dahl rats by 32 weeks of age. (C) Comparison of the occurrence of spontaneous bleeding episodes in Dahl-FVIII^−/− (inbred) to SD-FVIII^−/− (outbred) rats housed in our facility. SD-FVIII^−/− rats were developed by Nielsen et al¹⁹  using a zinc-finger nuclease strategy resulting in a 13 bp deletion in exon 16 of the F8 gene. (D) Percentage of Dahl-FVIII^−/− rats that experienced bleeding events by 32 weeks of age. (E) Percentage of SD-FVIII^−/− rats that experienced events by 32 weeks of age.