Mlc2v-Cre以性别偏差的方式诱导生殖线重组
Termeh Aslani1,2, Rimshah Abid1,2, Reshani Jeyaratnam1,3
1University of Ottawa Heart Institute, Ottawa, Ontario, Canada.
概括
用于心脏研究的Mlc2v-Cre小鼠,出乎意料地导致后代的生殖线重组. 这种非目标的Cre活动发生在两性中,但在女性中更频繁,导致全身基因变异.
科学领域:
- 心血管生物学 心血管生物学
- 遗传学 遗传学 是一个
- 发展生物学 发展生物学
背景情况:
- 在心脏研究中,Mlc2v-Cre小鼠系是用于心室特定基因向的广泛使用的工具.
- 在Mlc2v-Cre繁殖者的后代中观察到非肌肉组织中的意想不到的重组.
- 这表明了潜在的非目标CRE活动和生殖系传播,这可能会混实验结果.
研究的目的:
- 在Mlc2v-Cre小鼠中量化非目标Cre重组的流行率和性别依赖性.
- 调查来自Mlc2v-Cre繁殖者后代的无意基因向的程度.
- 突出在转基因小鼠模型中验证CRE重组特异性的必要性.
主要方法:
- Mlc2v-Cre小鼠与Rosa26tdTomato记者小鼠进行了交叉.
- 在产生的胚胎和生殖细胞中,可视化和分析了Cre-Lox重组.
- 在男性和女性生殖细胞中评估了MLC2V和tdTomato的表达.
主要成果:
- 在雄性和雌性育种者中,Mlc2v-Cre诱导了生殖线重组.
- 非目标重组发生在雌性繁殖者中更高的发病率.
- 这导致后代中无意产生的全身重组等位基因,独立于CRE转基因.
- 在男性和女性生殖细胞中检测到MLC2V和tdTomato表达,支持生殖系传播.
结论:
- Mlc2v-Cre小鼠系在两种性别中都表现出显著的非目标生殖系重组,对女性的性别依赖偏见显著.
- 这种现象可能导致后代的无意的全身基因向,从而损害了针对心室的研究的特异性.
- 研究人员必须严格验证CRE介导的重组特异性,以防止混实验结果,并确保在心脏和其他研究领域准确的数据解释.
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