Sequence of the murine factor VIII cDNA.

DNA clones corresponding to the mouse homolog of the human factor VIII gene have been isolated and sequenced. The murine gene is expressed in most tissues examined and the mRNA is approximately 1.8 kb smaller than the human transcript, primarily due to a shorter 3' untranslated region. The mouse cDNA encodes a protein of 2319 amino acids, 32 amino acids shorter than human factor VIII, with 74% identity to the human sequence. Further comparison shows that amino acid sequences in the functionally important A and C domains are highly conserved (84-93% identity), whereas the B domains and the two acidic domains are more divergent (42-70% identity). All thrombin/factor Xa cleavages sites and all but one activated protein C cleavage site are conserved in mouse factor VIII, as well as a tyrosine residue needed for von Willebrand factor binding. These findings suggest that mouse factor VIII operates in the clotting cascade much like the human protein, but reveal some differences that may have functional significance.