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Updated: Jul 20, 2025
Using Mouse Oocytes to Assess Human Gene Function During Meiosis I
Published on: April 10, 2018
Oocyte-specific Wee1-like protein kinase 2 is dispensable for fertility in mice
Kaori Nozawa1,2, Zian Liao1,2, Yuhkoh Satouh3,4
1Center for Drug Discovery, Baylor College of Medicine, Houston, TX, United States of America.
Abstract:
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.
Insights
Wee1-like protein kinase 2 (WEE2) loss-of-function in mice did not significantly impact fertility, suggesting alternative strategies for non-hormonal contraception development. Further research into gain-of-function or protein interactions is recommended.
Area of Science:
- Reproductive biology
- Molecular genetics
- Biochemistry
Background:
- Wee1-like protein kinase 2 (WEE2) is an oocyte-specific kinase crucial for meiotic arrest in human oocytes.
- WEE2 has been proposed as a target for non-hormonal female contraception.
- Pre-clinical models for WEE2 loss-of-function were previously unreported.
Purpose of the Study:
- To develop and characterize CRISPR/Cas9-generated knockout mouse models to investigate the role of WEE2 in female fertility.
- To assess the impact of WEE2 loss-of-function on oocyte meiotic arrest and overall reproductive success in mice.
Main Methods:
- Generation of two distinct Wee2 knockout mouse models utilizing CRISPR/Cas9 gene editing.
- Characterization of reproductive phenotypes, including litter size, litter production, and pup counts.
- Analysis of key reproductive parameters such as ovarian weight, oocyte maturation, and meiotic arrest.
Main Results:
- A frameshift mutation in exon 2 of Wee2 had no discernible effect on litter size, litter production, or oocyte meiotic arrest.
- A large deletion model of Wee2 knockout showed a minor reduction in pup numbers in homozygous females compared to heterozygotes.
- No significant differences were observed in ovarian weight, oocyte ovulation, or in vitro maturation rates between knockout and wild-type mice.
Conclusions:
- Loss-of-function of WEE2 in mice demonstrates minimal impact on overall female fecundity, likely due to biological redundancies.
- WEE2 loss-of-function is unlikely to be a viable strategy for non-hormonal contraception.
- Future contraceptive development targeting WEE2 should explore gain-of-function mechanisms or protein-protein interactions.
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