ABSTRACT. We report the sequence of a 2,779 base pair genomic DNA fragment containing the mouse glycoprotein (GP) Ibalpha gene. Similar to its human counterpart, the mouse GP Ibalpha gene contains a single exon encoding a 734-residue GP Ib\140 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 Ibalpha 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 olypeptide. The species-specific interaction between human GP Ibalpha 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 Ibalpha subunit. The results further define structural elements necessary for the interaction of human vWF and platelets.

Keywords: Platelet membrane glycoproteins, nucleotide sequence, blood platelets, hemostasis, thrombosis, von Willebrand factor.

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This is an up-to-date tabulation of all known mutations affecting the G6PD gene.

Reprint requests to: Tom Vulliamy, Ph.D., Department of Haematology, Hammersmith Hospital, Du Cane Road, London W12 ONN, phone: 81 383 2181, fax: 81 742 9335, e-mail: t.vulliamy@rpms.ac.uk.