Kitaguchi T, Murata M, Kuramochi T, Kobayashi K, Ito M, Ueyama Y, Nomura T, Hikichi K, Miyakawa Y, Handa M, Hiraoka Y, Aiso S, Ikeda Y
Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
Biochem Biophys Res Commun. 1996 Mar 18;220(2):418-24. doi: 10.1006/bbrc.1996.0420.
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.
血小板糖蛋白（GP）Ib/IX/V是血管性血友病因子（vWF）的异源寡聚体受体复合物，在高剪切应力条件下介导血小板黏附和聚集。它由GP Ib的α链和β链、GP IX以及GP V组成。为了建立携带人GP Ibα的转基因小鼠，我们将一个包含人GP Ibα基因的6 kb DNA片段注射到小鼠受精卵中，该片段包含完整的编码序列和假定的启动子区域。对113只后代进行筛选，仅发现1只表达人GP Ibα蛋白，并且已将人GP Ibα基因及其基因表达传递给下一代。人GP Ibα在转基因小鼠中的表达仅限于血小板和巨核细胞。在转基因小鼠血浆中未检测到糖甘蛋白，它是在正常人血浆中发现的人GP Ibα的蛋白水解片段。在瑞斯托菌素存在的情况下，人vWF支持转基因小鼠血小板的凝集，但不支持对照小鼠血小板的凝集。
