Loss of preimplantation embryo resulting from a Pum1 gene trap mutation.
Loss of preimplantation embryo resulting from a Pum1 gene trap mutation.
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DOI：
10.1016/j.bbrc.2015.04.019
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发表时间：
2015-06
影响因子：
3.1
通讯作者：
Chenwang Zhang;T. Zhu;Yanmei Chen;E. Xu
中科院分区：
文献类型：
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作者：
Chenwang Zhang;T. Zhu;Yanmei Chen;E. Xu
Pumilio是高度保守的RNA结合蛋白PUF家族的成员，在不同的动物物种中作为发育调节剂发挥作用。在哺乳动物中发现了两种Pumiliogenes，Pum 1和Pum 2，它们与精子发育、神经元发育以及人类疾病如神经变性有关。构建Pum蛋白不同部分的动物模型有助于进一步研究Pum蛋白的生理功能。在这里，我们描述了表征和分析的小鼠线拥有的基因陷阱突变thePumilio 1（Pum 1）基因。突变（Pum 1XE 002）纯合子小鼠不能在出生时或胚胎发育的不同时间点（E18、E14、E12）的成年后代中恢复。对植入前胚胎的仔细分析表明，在妊娠第3.5天没有检测到纯合囊胚。通过自然交配或杂合子之间的体外受精对1-细胞胚胎进行96小时的体外培养未能发现任何纯合囊胚，表明纯合植入前胚胎的早期丢失。Pum 1基因陷阱纯合子的缺乏表明Pum 1在非常早期的胚胎发育或受精中的作用。这种影响胚胎发育开始的新动物模型不仅有助于理解植入前胚胎发育的遗传机制，而且有助于理解发育和疾病中的翻译调控。
Pumilio is a member of the highly conserved PUF family of RNA-binding proteins that function as a developmental regulator in diverse animal species. TwoPumiliogenes,Pum1andPum2, have been identified in mammals and are found to be involved in sperm development, neuron development as well as human diseases such as neurodegeneration. Generation of animal models disrupting different parts of Pum protein could help to further dissect their physiological function. Here we described characterization and analysis of a mouse line possessing a gene trap mutation of thePumilio1(Pum1) gene. Mice homozygous for the mutation (Pum1XE002) cannot be recovered in the adult offspring, at birth or at different time points of embryonic development (E18, E14, E12). Careful analysis of preimplantation embryos showed that no homozygous blastocysts could be detected on day 3.5 of gestation. 96-hr in vitro culture of 1-cell embryos either by natural mating or in vitro fertilization between heterozygotes failed to uncover any homozygous blastocysts, suggesting an early loss of homozygous preimplantation embryos. The lack ofPum1gene trap homozygotes suggests a role ofPum1in very early embryonic development or fertilization. This novel animal model affecting the beginning of embryonic development could help to understand not only the genetic mechanism underlying preimplantation embryonic development but also the translational regulation in development and diseases.