Bogliotti Yanina S, Vilarino Marcela, Ross Pablo J
Department of Animal Science, University of California, Davis.
Department of Animal Science, University of California, Davis;
J Vis Exp. 2016 Oct 5(116):54465. doi: 10.3791/54465.
Cytoplasmic microinjection into one-cell embryos is a very powerful technique. As an example, it enables the delivery of genome editing tools that can create genetic modifications that will be present in every cell of an adult organism. It can also be used to deliver siRNA, mRNAs or blocking antibodies to study gene function in preimplantation embryos. The conventional technique for microinjecting embryos used in rodents consists of a very thin micropipette that directly penetrates the plasma membrane when advanced into the embryo. When this technique is applied to livestock animals it usually results in low efficiency. This is mainly because in contrast to mice and rats, bovine, ovine, and porcine zygotes have a very dark cytoplasm and a highly elastic plasma membrane that makes visualization during injection and penetration of the plasma membrane hard to achieve. In this protocol, we describe a suitable microinjection method for the delivery of solutions into the cytoplasm of cattle zygotes that has proved to be successful for sheep and pig embryos as well. First, a laser is used to create a hole in the zona pellucida. Then a blunt-end glass micropipette is introduced through the hole and advanced until the tip of the needle reaches about 3/4 into the embryo. Then, the plasma membrane is broken by aspiration of cytoplasmic content inside the needle. Finally, the aspirated cytoplasmic content followed by the solution of interest is injected back into the embryonic cytoplasm. This protocol has been successfully used for the delivery of different solutions into bovine and ovine zygotes with 100% efficiency, minimal lysis, and normal blastocysts development rates.
向单细胞胚胎进行细胞质显微注射是一项非常强大的技术。例如,它能够递送基因组编辑工具,从而产生将存在于成年生物体每个细胞中的基因修饰。它还可用于递送小干扰RNA、信使核糖核酸或阻断抗体,以研究植入前胚胎中的基因功能。啮齿动物中用于胚胎显微注射的传统技术是使用一根非常细的微量移液器,当推进到胚胎中时直接穿透质膜。当将该技术应用于家畜时,其效率通常较低。这主要是因为与小鼠和大鼠相比,牛、羊和猪的受精卵具有非常暗的细胞质和高度弹性的质膜,这使得在注射过程中进行可视化以及穿透质膜变得很难实现。在本方案中,我们描述了一种将溶液递送至牛受精卵细胞质的合适显微注射方法,该方法已证明对绵羊和猪胚胎也同样成功。首先,使用激光在透明带中创建一个孔。然后将钝头玻璃微量移液器通过该孔插入并推进,直到针尖到达胚胎约四分之三处。然后,通过吸取针内的细胞质内容物来打破质膜。最后,将吸取的细胞质内容物以及感兴趣的溶液注射回胚胎细胞质中。该方案已成功用于以100%的效率、最小的裂解率和正常的囊胚发育率将不同溶液递送至牛和羊的受精卵中。