ESTABLISHMENT AND CHARACTERIZATION OF TRANSGENIC MICE EXPRESSING HUMAN PLATELET GLYCOPROTEIN IB-ALPHA

The platelet glycoprotein (GP) Ib/IX/V is a hetero-oligomeric receptor complex for von Willebrand factor (vWF) and mediates platelet adhesio n and aggregation under high shear stress conditions. It is composed o f alpha and beta chain of GP Ib, GP IX, AND and GP V. To establish tra nsgenic mice carrying human GP Ib alpha, we injected into mouse zygote s a 6 kb DNA fragment containing human GP Ib alpha gene that included entire coding sequence and putative promoter region. One hundred and t hirteen offsprings were screened, and only one was found to express hu man GP Ib alpha protein and has passed the human GP Ib alpha gene as w ell as the expression of the gene to next generation. The expression o f human GP Ib alpha in transgenic mice was limited to platelets and me gakaryocytes. Glycocalicin, a proteolytic fragment of human GP Ib alph a found in normal human plasma, was not detected in transgenic mouse p lasma. Human vWF in the presence of ristocetin supported agglutination of transgenic mouse platelets, but not of control mouse platelets. (C ) 1996 Academic Press, Inc.