Lin H F, Maeda N, Smithies O, Straight D L, Stafford D W
Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-3280, USA.
Blood. 1997 Nov 15;90(10):3962-6.
Coagulation factor IX deficiency causes hemophilia B in humans. We have used gene targeting to develop a coagulation factor IX-deficient (factor IX-knockout) mouse strain. Mouse embryonic stem (ES) cells were targeted by a socket-containing vector that replaces the promoter through exon 3 of the factor IX gene by neoDeltaHPRT, which is a functional neo gene plus a partially deleted hypoxanthine phosphoribosyl transferase minigene. Chimeric mice generated using these socket-containing ES cells transmitted the targeted factor IX gene to their female offspring. Male offspring from these females were characterized and shown to exhibit a phenotype similar to hemophilia B. This factor IX-deficient mouse strain will be useful for studying gene therapy methods and structure-function relationships of recombinant factor IX proteins in vivo.
凝血因子IX缺乏会导致人类患血友病B。我们利用基因打靶技术培育出了一种凝血因子IX缺陷（因子IX基因敲除）小鼠品系。小鼠胚胎干细胞（ES细胞）被一种含套接载体靶向，该载体通过neoDeltaHPRT取代因子IX基因从启动子到外显子3的部分，neoDeltaHPRT是一个功能性新霉素基因加上一个部分缺失的次黄嘌呤磷酸核糖基转移酶小基因。使用这些含套接ES细胞产生的嵌合小鼠将靶向的因子IX基因传递给了它们的雌性后代。对这些雌性后代的雄性后代进行了特征分析，结果显示它们表现出与血友病B相似的表型。这种因子IX缺陷小鼠品系将有助于研究体内基因治疗方法以及重组因子IX蛋白的结构-功能关系。
