F8 and hemophilia A: As mechanistic studies testing the role of genes in immunity to FVIII in patients with hemophilia A are not feasible, preclinical models of hemophilia A that encode the same F8 pathogenic variant and Major Histocompatibility Complex (MHC) haplotype but are on disparate genetic backgrounds [C57BL/6J (B6) versus mixed S129/B6 (129S4/SvJae + B6)] (35, 36) were employed.