不同小鼠品系囊胚受体对C57BL/6胚胎干细胞种系嵌合效率的影响  

Impact of different mouse blastocyst donors on the efficiency of germline chimera production from C57BL/6 embryonic stem cells

作　　者：周舒雅[1] 左琴[1] 刘甦苏[1] 王辰飞 李保文[1] 贺争鸣[1] 范昌发[1] 

机构地区：[1]中国食品药品检定研究院实验动物资源研究所,国家啮齿类实验动物种子中心,北京100050 [2]北京百奥赛图基因生物技术有限公司,北京101111

出　　处：《中国实验动物学报》2015年第4期353-358,共6页Acta Laboratorium Animalis Scientia Sinica

基　　金：国家自然科学基金青年科学基金项目(编号:81401661)

摘　　要：目的考察不同品系的小鼠囊胚对C57BL/6胚胎干细胞种系嵌合效率的影响,进而提高通过在C57BL/6胚胎干细胞中同源重组制作基因打靶小鼠的效率。方法选取近交系B6(Cg)-Tyrc-2J和BALB/c品系及封闭群ICR作为囊胚供体鼠,通过在TLX3、Ai3K和SL三个不同基因修饰ES细胞的种系嵌合实验中,平行比较三者的囊胚利用率、嵌合鼠获得效率以及种系遗传效率等三个方面,并进一步针对囊胚来源这一因素对效率的影响进行统计学分析。结果三种ES细胞均未能通过B6(Cg)-Tyrc-2J品系囊胚的注射获得种系遗传。而BALB/c品系与ICR品系相比,囊胚利用率明显低于ICR品系(P<0.05);嵌合鼠获得效率方面,BALB/c与ICR相当(P=0.115);而种系遗传效率方面,BALB/c品系显著高于其他品系(P<0.01)。结论 BALB/c品系在C57BL/6胚胎干细胞种系嵌合效率方面确实具有优势,然而,由于BALB/c囊胚较难获得,并且存在发育延迟和透明带脆性高等问题,而ICR品系在囊胚获得和利用方面的效率明显高于BABL/c,并且也可以支持C57BL/6胚胎干细胞的种系遗传,因此也是C57BL/6胚胎干细胞囊胚注射中较好的选择。Objective To improve the gene targeting efficiency with C57BL/6 embryonic stem（ ES） cells. Methods Three different genetically modified C57 BL /6 ES cell lines,named TLX3,Ai3 K and SL,were microinjected into ICR,B6（ Cg）-Tyrc-2Jand BALB / c mouse blastocysts,respectively. The efficiency was statistically evaluated according to three aspects： blastocyst collection,chimera production and germline transmission. Results None of the three ES cell lines was germline transmitted with B6（ Cg）-Tyrc-2Jmice as blastocyst donors,while it was achieved with both BALB / c and ICR mouse blastocysts. Compared in the aspect of blastocysts collection,ICR mouse was much better than BALB / c mouse（ P〈0. 05）,and the chimera production efficiency of ICR mouse was comparable to that of BALB/c mouse（ P = 0. 115）.As to the germline transmission efficiency,that of BALB / c mice is significantly higher than that of the ICR mice（ P〈0. 01）. Conclusions The germline transmission efficiency of BALB / c mouse is highest among these three mouse strains.However,it has the disadvantages of blastocyst collection,developmental delay and zona pellucida fragility,compared with ICR mouse. Therefore,ICR mouse is also a good candidate as blastocyst donor for embryonic stem cell microinjection.

关 键 词：C57BL/6胚胎干细胞 BALB/c囊胚 ICR囊胚 B6(Cg)-Tyr^c-2J囊胚 种系嵌合效率 

分 类 号：Q95-33[生物学—动物学]