Platelet-induced expression of FIX (2bF9) is not as effective as 2bF8 in the inhibitor model. (A) Two transgenic lines of mice were developed that expressed FIX in megakaryocytes and stored FIX in platelet α-granules. The 2bF9 high line (2bF9-H) was equivalent to 20% of normal circulating FIX, and the 2bF9 low line (2bF9-L) corresponded to 1% of normal circulating FIX. Both 2bF9-L and 2bF9-H survived tail-clip challenge similar to wild-type mice. The FIX^null and FIX^null mice infused with 1.6 IU/dL plasma did not survive tail-clip challenge. (B) 2bF9-H mice were subjected to tail-clip challenge in the presence or absence of inhibitory antibody to FIX. Even the 2bF9-H mice had minimal survival when challenged with low or moderate inhibitory antibody. Because these mice have circulating levels at 20% of normal circulating FIX, there is not similar protection from 2bF9 similar to that seen in 2bF8 mice with 1.23% levels of FVIII. Compare results with those for hemophilia A in Figure 3B.