title: Establishment and characterization of transgenic mice expressing human platelet glycoprotein Ib alpha.
abstract: The platelet glycoprotein (GP) Ib/IX/V is a hetero-oligomeric receptor complex for von Willebrand factor (vWF) and mediates platelet adhesion and aggregation under high shear stress conditions. It is composed of alpha and beta chain of GP Ib, GP IX, AND and GP V. To establish transgenic mice carrying human GP Ib alpha, we injected into mouse zygotes a 6 kb DNA fragment containing human GP Ib alpha gene that included entire coding sequence and putative promoter region. One hundred and thirteen offsprings were screened, and only one was found to express human GP Ib alpha protein and has passed the human GP Ib alpha gene as well as the expression of the gene to next generation. The expression of human GP Ib alpha in transgenic mice was limited to platelets and megakaryocytes. Glycocalicin, a proteolytic fragment of human GP Ib alpha found in normal human plasma, was not detected in transgenic mouse plasma. Human vWF in the presence of ristocetin supported agglutination of transgenic mouse platelets, but not of control mouse platelets.
authors.affiliation: Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Kitaguchi
authors.forename: M
authors.initials: M
authors.lastname: Murata
authors.forename: T
authors.initials: T
authors.lastname: Kuramochi
authors.forename: K
authors.initials: K
authors.lastname: Kobayashi
authors.forename: M
authors.initials: M
authors.lastname: Ito
authors.forename: Y
authors.initials: Y
authors.lastname: Ueyama
authors.forename: T
authors.initials: T
authors.lastname: Nomura
authors.forename: K
authors.initials: K
authors.lastname: Hikichi
authors.forename: Y
authors.initials: Y
authors.lastname: Miyakawa
authors.forename: M
authors.initials: M
authors.lastname: Handa
authors.forename: Y
authors.initials: Y
authors.lastname: Hiraoka
authors.forename: S
authors.initials: S
authors.lastname: Aiso
authors.forename: Y
authors.initials: Y
authors.lastname: Ikeda
mesh_terms: D000818:Animals; D001483:Base Sequence; D015139:Blotting, Southern; D015153:Blotting, Western; D005434:Flow Cytometry; D015870:Gene Expression; D006801:Humans; D008533:Megakaryocytes / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000235:genetics* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012310:Ristocetin / Q000494:pharmacology; D014841:von Willebrand Factor / Q000494:pharmacology
chemical_list: D010975:Platelet Aggregation Inhibitors; D019038:Platelet Glycoprotein GPIb-IX Complex; C023592:glycocalicin; D014841:von Willebrand Factor; D012310:Ristocetin