Expression of human platelet glycoprotein Ib alpha in transgenic mice.
Platelets are cytoplasmic fragments of megakaryocytes and, therefore, their membrane proteins cannot be manipulated by expression methods in culture. To overcome this limitation, we have expressed human glycoprotein (GP) Ib alpha in transgenic mouse megakaryocytes and found that it was present on the surface of platelets associated with the mouse GP Ib beta subunit. This finding demonstrates that assembly of the heterooligomeric GP Ib complex occurs through mechanisms conserved across species. In contrast, the receptor function of GP Ib exhibited restricted species specificity, since only the chimeric complex containing human GP Ib alpha bound human von Willebrand factor and supported platelet aggregation mediated by ristocetin. These studies demonstrate the transgenic engineering of a platelet adhesion receptor under control of the human GP Ib alpha promoter and illustrate a new approach to manipulate platelet receptors and study structure-function relationships in hemostasis and thrombosis.
Ware
J
J
Roon Research Center for Arteriosclerosis and Thrombosis, Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, California 92037.
Russell
S R
SR
Marchese
P
P
Ruggeri
Z M
ZM
D000818:Animals; D000911:Antibodies, Monoclonal; D001792:Blood Platelets / Q000502:physiology*; D001853:Bone Marrow / Q000502:physiology*; D001854:Bone Marrow Cells; D004247:DNA / Q000235:genetics; D005340:Fibrinogen / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D015870:Gene Expression; D006801:Humans; D007700:Kinetics; D008533:Megakaryocytes / Q000166:cytology / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D010980:Platelet Membrane Glycoproteins / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D015183:Restriction Mapping; D014841:von Willebrand Factor / Q000378:metabolism
D000911:Antibodies, Monoclonal; D010980:Platelet Membrane Glycoproteins; D014841:von Willebrand Factor; D005340:Fibrinogen; D004247:DNA