叶酸代谢的突变导致表观遗传不稳定性和对发育发展的跨代影响
Nisha Padmanabhan1, Dongxin Jia, Colleen Geary-Joo
1Centre for Trophoblast Research, Department of Physiology, Development, and Neuroscience, University of Cambridge, Cambridge CB2 3EG, UK.
Cell
|October 1, 2013
概括
孕产妇的叶酸代谢对于发育至关重要. 甲氨酸合成酶减少酶 (Mtrr) 的突变导致发育缺陷和表观遗传变化,影响后代几代人.
科学领域:
- 发育生物学 发展生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 遗传学 是一个遗传学.
背景情况:
- 母亲的叶酸摄入量对胎儿发育至关重要,但潜在的分子机制尚不清楚.
- 甲氨酸合成酶减少酶 (Mtrr) 是叶酸代谢中的一个关键酶,对于甲基组转移至关重要.
- 了解Mtrr的作用对于破译依赖叶酸的发育途径至关重要.
研究的目的:
- 研究将叶酸代谢与胚胎和胎儿发育联系起来的分子机制.
- 确定Mtrr基因突变对发育过程的影响.
- 探索Mtrr缺乏的跨代影响的潜力.
主要方法:
- 在小鼠Mtrr基因中产生了低形态突变.
- 分析了包括生长,先天性形和胎盘缺陷在内的发育现象.
- 利用胚胎移植实验将母体环境影响与直接遗传/表观遗传分开.
- 评估了受影响组织中的表观遗传不稳定性和基因表达变化.
主要成果:
- 由于MTRR缺乏,导致子宫内生长受限,发育延迟,神经管,心脏和胎盘的缺陷.
- 发育缺陷受到母亲祖父母的Mtrr基因型的影响.
- 表观遗传不稳定性和基因表达的改变被观察到来自Mtrr缺陷母方祖父母的野生类型后代的胎盘中.
- 由于MTRR缺乏,导致母体环境依赖的生长缺陷和独立的先天性形持续五代.
结论:
- 在哺乳动物发育中,Mtrr起着至关重要的作用,突变导致严重的缺陷.
- 发育结果受到父母和祖父母的基因型的影响,这表明复杂的遗传模式.
- Mtrr缺乏的跨代表观遗传影响了多代人,突出了代谢干扰的长期后果.
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