Cloning of the Murine Platelet Glycoprotein Ibα Gene Highlighting Species-Specific Platelet Adhesion,

ABSTRACT: We report the sequence of a 2,779 base pair genomic DNA fragment containing the mouse glycoprotein (GP) Ibα gene. Similar to its human counterpart, the mouse GP Ibα gene contains a single exon encoding a 734-residue GP Ibα precursor polypeptide. Comparative analysis between human and mouse polypeptides reveals a 75% sequence similarity between the amino-terminal domain of each polypeptide. However, there is sequence divergence within a short linear sequence of the amino-terminal domain previously implicated in human GP Ibα as critical for the binding of human von Willebrand factor (vWF). Mouse and human primary sequences diverge through their extracytoplasmic macroglycopeptide domains reducing the overall sequence similarity to 70%. The transmembrane and cytoplasmic sequences are highly conserved in both species with 59 identical residues among the 62 comprising the carboxyl-terminus of each polypeptide. The species-specific interaction between human GP Ibα 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 human GP Ibα subunit. The results further define structural elements necessary for the interaction of human vWF and platelets.