Swick A G, Janicot M, Cheneval-Kastelic T, McLenithan J C, Lane M D
Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
Proc Natl Acad Sci U S A. 1992 Mar 1;89(5):1812-6. doi: 10.1073/pnas.89.5.1812.
Heterologous proteins can be expressed in Xenopus laevis oocytes by cytoplasmic microinjection of mRNA. To circumvent limitations inherent in this approach we investigate direct nuclear injection of strong viral expression vectors to drive transcription and subsequent translation of cDNAs encoding cytoplasmic, secreted, and plasma membrane proteins. After several viral promoters had been tested, the pMT2 vector was found to be a superior expression vector for X. laevis oocytes capable of directing expression of high levels of functional heterologous proteins. Typically the amount of protein derived from transcription-translation of the microinjected cDNA accounts for approximately 1% of total non-yolk protein. Moreover, the inefficiency usually associated with nuclear injections was overcome by coinjection of pMT2 driving expression of a secreted alkaline phosphatase as an internal control to select positive-expressing oocytes. Using this method, we have successfully expressed high levels of chloramphenicol acetyltransferase, the adipocyte-specific cytosolic 422(aP2) protein, and the membrane-associated glucose transporter GLUT1. The system described should be applicable to a wide variety of proteins for which cDNAs are available. Hence, the cumbersome and often inefficient in vitro synthesis of mRNA for studying ion channels, receptors, and transporters as well as for expression cloning in Xenopus oocytes should no longer be necessary.
通过向非洲爪蟾卵母细胞的细胞质显微注射mRNA可表达异源蛋白。为了克服这种方法固有的局限性,我们研究了直接向细胞核注射强大的病毒表达载体,以驱动编码细胞质、分泌型和质膜蛋白的cDNA的转录及随后的翻译。在测试了几种病毒启动子后,发现pMT2载体是用于非洲爪蟾卵母细胞的优良表达载体,能够指导高水平功能性异源蛋白的表达。通常,源自显微注射cDNA转录-翻译的蛋白量约占总非卵黄蛋白的1%。此外,通过共注射驱动分泌型碱性磷酸酶表达的pMT2作为内部对照来选择阳性表达的卵母细胞,克服了通常与核注射相关的低效问题。使用这种方法,我们成功地高水平表达了氯霉素乙酰转移酶、脂肪细胞特异性胞质蛋白422(aP2)以及膜相关葡萄糖转运蛋白GLUT1。所述系统应适用于有cDNA可用的多种蛋白。因此,为研究离子通道、受体和转运蛋白以及在非洲爪蟾卵母细胞中进行表达克隆而进行的繁琐且往往低效的mRNA体外合成应该不再必要。