通过CRISPR-Cas9介导的超门德尔遗传在雌性小鼠生殖系中
Hannah A Grunwald1, Valentino M Gantz1, Gunnar Poplawski2,3
1Division of Biological Sciences, Section of Cellular and Developmental Biology, University of California, San Diego, La Jolla, CA, USA.
Nature
|January 25, 2019
概括
研究人员在小鼠中开发了CRISPR-Cas9基因驱动系统,通过纠正雌性生殖系中的DNA断裂,成功地改变了遗传. 这一突破使得复杂的基因型能够快速生成,
科学领域:
- 遗传学
- 分子生物学
- 发育生物学
背景情况:
- 基因驱动系统偏向遗传,使得快速的基因型产生.
- 通过CRISPR-Cas9技术, 能够有效地驱动昆虫的基因.
- 之前试图在哺乳动物中制造基因驱动器是没有成功的.
研究的目的:
- 在早期小鼠胚胎和生殖系中评估CRISPR-Cas9介导的基因转换.
- 确定同质导向修复是否可用于哺乳动物的基因驱动.
- 建立一种快速生成小鼠复杂基因型的方法.
主要方法:
- 一个编码导向RNA的活跃基因元素嵌入了小鼠的铁酶 (Tyr) 基因.
- 在早期胚胎和正在发育的雄性和雌性生殖系中表达CRISPR- Cas9.
- 通过分析DNA断裂纠正和遗传模式来评估同质导向修复.
主要成果:
- 在早期胚胎和男性生殖系中,CRISPR-Cas9诱导了双链DNA断裂,但这些并未通过同源导向修复得到修复.
- 仅限于雌性生殖系的Cas9表达导致双链断裂通过同质导向修复得到纠正.
- 这种纠正将活跃的基因元素复制到受体染色体上,增加了它的遗传率.
结论:
- 在雌性小鼠的生殖系中,CRISPR-Cas9介导的基因转换是可行的.
- 这种系统成功地偏向了小鼠所需的等位基因的遗传.
- 这项技术有可能彻底改变生物医学研究中的动物模型.
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