在器官生成过程中NAD缺乏的时间决定了缺陷类型和透率
Kayleigh Bozon1,2, Hartmut Cuny1,3, Nana Sunn4
1Developmental and Stem Cell Division, Victor Chang Cardiac Research Institute, Sydney, NSW, Australia.
概括
遗传性NAD缺乏障碍 (CNDD) 导致由于低胚胎尼古丁胺胺氨基二核酸 (NAD) 的出生缺陷. 怀孕早期母亲的NAD前体水平会影响胚胎生长和形严重程度,这表明NAD代谢物作为预测生物标志物.
科学领域:
- 发展生物学 发展生物学
- 生物化学 生物化学
- 遗传学 遗传学 是一个
背景情况:
- 主要的先天性形往往缺乏明确的原因,源于复杂的遗传和环境相互作用.
- 先天性NAD缺陷障碍 (CNDD) 导致多种形和胚胎损失,即使在具有相同遗传变异的兄弟姐妹中也显示出可变的结果.
- 鼠标模型表明,由于胚胎合成受损或母体NAD前体供应不足而导致的胚胎尼古丁胺胺氨基二核酸 (NAD) 缺乏的CNDD结果.
研究的目的:
- 为了确定胚胎对CNDD形的敏感性的关键时间.
- 调查导致CNDD形变异的因素.
- 在CNDD中建立母体NAD代谢和胚胎发育之间的联系.
主要方法:
- 在野生型小鼠中通过操纵母体饮食诱导的CNDD.
- 在子宫内长度监测受影响和未受影响的胚胎.
- 相关的母体血液NAD代谢组 (通过质谱测量) 与胚胎表型 (通过MRI和微CT评估) 每隔3天.
主要成果:
- 形在子之间有所不同,并且与不同的胚胎生长动态相关.
- 从胚胎第6.5天起,来自母亲的胚胎具有较低的NAD救援途径代谢物和最小的分泌代谢物,体积较小,缺陷较多.
- 改变胚胎生长和减少母体在器官生成期间的NAD前体可用性被确定为CNDD的原因.
结论:
- 在CNDD中的胚胎表型与在器官生成期间和之前母亲的NAD前体可用性直接相关.
- 孕产妇代谢干扰时间的变化与各种器官和组织缺陷类型有关.
- 从NAD衍生的代谢物显示出作为CNDD预测生物标志物的潜力.
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