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卵细胞特异性Wee1-样蛋白激酶2对于小鼠的生育是不可或缺的

Kaori Nozawa^1,2, Zian Liao^1,2, Yuhkoh Satouh^3,4

¹Center for Drug Discovery, Baylor College of Medicine, Houston, TX, United States of America.

|August 1, 2023

概括

在小鼠中,WEE2-样蛋白激酶2 (WEE2) 功能丧失没有显著影响生育能力,这表明了非激素避孕药开发的替代策略. 建议对功能增益或蛋白质相互作用进行进一步的研究.

科学领域:

生殖生物学生殖生物学
分子遗传学分子遗传学
生物化学生物化学

背景情况:

类似Wee1的蛋白激酶2 (WEE2) 是一种特定于卵细胞的激酶,对人类卵细胞中介性停止至关重要.
已提出WEE2作为非荷尔蒙女性避孕的目标.
以前没有报告WEE2功能丧失的临床前模型.

研究的目的:

开发和描述CRISPR/Cas9生成的淘汰赛小鼠模型,以调查WEE2在女性生育中的作用.
评估WEE2功能丧失对卵细胞介质停止和小鼠整体生殖成功的影响.

主要方法:

使用CRISPR/Cas9基因编辑生成两个不同的Wee2淘汰赛小鼠模型.
生殖表型的表征,包括 litter 尺寸, litter 生产和幼数量.
分析关键的生殖参数,如卵巢体重,卵细胞成熟和介质停止.

主要成果:

在Wee2的exon 2中发生的框架转移突变对 litter 尺寸, litter 生产或卵细胞介质停止没有明显的影响.
一个Wee2淘汰的大型删除模型显示,同卵性雌性与异卵性雌性相比,幼数量略有减少.
在淘汰赛和野生类型小鼠之间,没有观察到卵巢体重,卵细胞排卵或体外成熟率的显著差异.

结论:

在小鼠中,WEE2的功能丧失对女性的整体生育能力的影响很小,可能是由于生物冗余.
WEE2功能丧失不太可能成为非激素避孕的可行策略.
针对WEE2的未来避孕药开发应该探索功能获取机制或蛋白质-蛋白质相互作用.

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