CLONING OF THE MURINE PLATELET GLYCOPROTEIN IB-ALPHA GENE HIGHLIGHTING SPECIES-SPECIFIC PLATELET-ADHESION

We report the sequence of a 2,779 base pair genomic DNA fragment conta ining the mouse glycoprotein (GP) Ib alpha gene, Similar to its human counterpart, the mouse GP Ib alpha gene contains a single exon encodin g a 734-residue GP Ib alpha precursor polypeptide, Comparative analysi s between human and mouse polypeptides reveals a 75% sequence similari ty between the amino-terminal domain of each polypeptide, However, the re is sequence divergence within a short linear sequence of the amino- terminal domain previously implicated in human GP Ib alpha as critical for the binding of human von Willebrand factor (VWF). Mouse and human primary sequences diverge through their extracytoplasmic macroglycope ptide domains reducing the overall sequence similarity to 70%. The tra nsmembrane and cytoplasmic sequences are highly conserved in both spec ies with 59 identical residues among the 62 comprising the carboxyl-te rminus of each polypeptide. The species-specific interaction between h uman GP Iba and vWF was demonstrated in a model flow system monitoring the ability of surface-bound human vWF to capture from flowing blood normal mouse platelets or transgenic mouse platelets expressing the hu man GP Iba subunit, The results further define structural elements nec essary for the interaction of human vWF and platelets.