INTEGRATION AND GERM-LINE TRANSMISSION OF A PSEUDOTYPED RETROVIRAL VECTOR IN ZEBRAFISH

INTEGRATION AND GERM-LINE TRANSMISSION OF A PSEUDOTYPED RETROVIRAL VECTOR IN ZEBRAFISH
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DOI:
10.1126/science.8036514
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发表时间:
1994-07-29
期刊:
影响因子:
56.9
通讯作者:
HOPKINS, N
HOPKINS, N
中科院分区:
综合性期刊1区
文献类型:
--
作者:
LIN, S;GAIANO, N;HOPKINS, N

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斑马鱼是胚胎学研究和遗传分析的理想模型,因此它正迅速成为脊椎动物发育研究的流行模式系统。为了确定用水泡性口炎病毒的包膜糖蛋白假型化的逆转录病毒载体是否可以感染斑马鱼胚胎,特别是注定成为生殖系的细胞,将假型化的病毒注射到囊胚期斑马鱼胚胎中。51个胚胎被允许发育,8个将前病毒DNA传递给它们的后代。创始人是嵌合体,但正如预期的那样,转基因F-1的传递前病毒DNA在孟德尔的方式到F-2后代。转基因F-1鱼遗传了一个单一的整合前病毒,一个单一的创始人可以传递一个以上的病毒整合到它的后代。这些结果表明,这种泛热带假型载体,最初开发的人类基因治疗,将使逆转录病毒载体在斑马鱼中的使用成为可能。
The zebrafish is rapidly becoming a popular model system for the study of vertebrate development because it is ideal for both embryological studies and genetic analysis. To determine if a retroviral vector pseudotyped with the envelope glycoprotein of the vesicular stomatitis virus could infect zebrafish embryos, and in particular, the cells destined to become the germ line, a pseudotyped virus was injected into blastula-stage zebrafish embryos. Fifty-one embryos were allowed to develop and eight transmitted proviral DNA to their progeny. Founders were mosaic, but as expected, transgenic F-1's transmitted proviral DNA in a Mendelian fashion to the F-2 progeny. Transgenic F-1 fish inherited a single integrated provirus, and a single founder could transmit more than one viral integration to its progeny. These results demonstrate that this pantropic pseudotyped vector, originally developed for human gene therapy, will make the use of retroviral vectors in zebrafish possible.