Oocyte-specific Wee1-like protein kinase 2 is dispensable for fertility in mice

被引:1
|
作者
Nozawa, Kaori [1 ,2 ]
Liao, Zian [1 ,2 ]
Satouh, Yuhkoh [3 ,4 ]
Geng, Ting [1 ,2 ]
Ikawa, Masahito [3 ,5 ]
Monsivais, Diana [1 ,2 ]
Matzuk, Martin M. [1 ,2 ,6 ,7 ]
机构
[1] Baylor Coll Med, Ctr Drug Discovery, Houston, TX 77030 USA
[2] Baylor Coll Med, Dept Pathol & Immunol, Houston, TX 77030 USA
[3] Osaka Univ, Res Inst Microbial Dis, Dept Expt Genome Res, Suita, Osaka, Japan
[4] Gunma Univ, Inst Mol & Cellular Regulat, Maebashi, Gunma, Japan
[5] Univ Tokyo, Inst Med Sci, Minato ku, Tokyo, Japan
[6] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA
[7] Baylor Coll Med, Dept Biochem & Mol Pharmacol, Houston, TX 77030 USA
来源
PLOS ONE | 2023年 / 18卷 / 08期
基金
日本学术振兴会;
关键词
MEIOTIC RESUMPTION; MOUSE OOCYTE; WEE1B; FERTILIZATION; MEIOSIS; ARREST; EMI2;
D O I
10.1371/journal.pone.0289083
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Wee1-like protein kinase 2 (WEE2) is an oocyte-specific protein tyrosine kinase involved in the regulation of oocyte meiotic arrest in humans. As such, it has been proposed as a candidate for non-hormonal female contraception although pre-clinical models have not been reported. Therefore, we developed two novel knockout mouse models using CRISPR/Cas9 to test loss-of-function of Wee2 on female fertility. A frameshift mutation at the Wee2 translation start codon in exon 2 had no effect on litter size, litter production, or the ability of oocytes to maintain prophase I arrest. Because of the lack of a reproductive phenotype, we additionally generated a Wee2 allele with a large deletion by removing all coding exons. While there was no difference in the total number of litters produced, homozygous Wee2 female knockout mice with the larger deletion produced fewer pups than heterozygous littermates. Furthermore, there was no difference for key reproductive parameters measured in the mouse models, including ovarian weight, number of ovulated oocytes, or oocytes that underwent in vitro maturation. Therefore, as loss of Wee2 in mice shows only minor effects on overall fecundity, contraceptive development with WEE2 should consider exploiting alternative properties such as gain-of-function or protein-protein interactions, as Wee2 loss-of-function is likely complicated by biological redundancies with other proteins co-expressed in oocytes.
引用
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页数:13
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