FVIII in plasma and platelets in 2bF8-transgenic mice. Transgenic mice were developed with the cDNA for B domain-deleted FVIII placed under the control of the integrin α-IIb promoter and bred onto the murine FVIII^null background. These transgenic mice (2bF8) only expressed FVIII in megakaryocytes and stored FVIII together with VWF in platelets. (A) Plasma FVIII was measured and was present in wild-type (WT), but was absent in plasma from either FVIII^null or 2bF8 transgenic (FVIII^null) mice. (B) Platelet FVIII was measured in murine platelets and was absent in wild-type and FVIII^null mice; but, in 2bF8 transgenic mice, platelet FVIII was present and was greater in homozygous transgenic mice (2bF8^trans+/+) than in heterozygous (2bF8^trans+/–) mice. To determine the effect of VWF on the expression of FVIII in platelets, the 2bF8 transgene was bred onto the double KO background (FVIII^null VWF^null). Platelet FVIII expression was reduced in the absence of VWF. Bone marrow transplantation (BMT) from a heterozygous 2bF8 mouse conferred similar expression levels when transplanted into FVIII^null mice following ablative bone marrow conditioning. In data not illustrated in this figure, platelet FVIII conferred survival following tail-clip challenge in contrast to the FVIII^null mice in which this challenge was uniformly fatal. *P < .001. (Used with permission, with full details provided in J Clin Invest. 2006;116:1974-1982.)