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

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 develop...

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Autores principales: Nozawa, Kaori, Liao, Zian, Satouh, Yuhkoh, Geng, Ting, Ikawa, Masahito, Monsivais, Diana, Matzuk, Martin M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10393137/
https://www.ncbi.nlm.nih.gov/pubmed/37527245
http://dx.doi.org/10.1371/journal.pone.0289083
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author Nozawa, Kaori
Liao, Zian
Satouh, Yuhkoh
Geng, Ting
Ikawa, Masahito
Monsivais, Diana
Matzuk, Martin M.
author_facet Nozawa, Kaori
Liao, Zian
Satouh, Yuhkoh
Geng, Ting
Ikawa, Masahito
Monsivais, Diana
Matzuk, Martin M.
author_sort Nozawa, Kaori
collection PubMed
description 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.
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spelling pubmed-103931372023-08-02 Oocyte-specific Wee1-like protein kinase 2 is dispensable for fertility in mice Nozawa, Kaori Liao, Zian Satouh, Yuhkoh Geng, Ting Ikawa, Masahito Monsivais, Diana Matzuk, Martin M. PLoS One Research Article 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. Public Library of Science 2023-08-01 /pmc/articles/PMC10393137/ /pubmed/37527245 http://dx.doi.org/10.1371/journal.pone.0289083 Text en © 2023 Nozawa et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Nozawa, Kaori
Liao, Zian
Satouh, Yuhkoh
Geng, Ting
Ikawa, Masahito
Monsivais, Diana
Matzuk, Martin M.
Oocyte-specific Wee1-like protein kinase 2 is dispensable for fertility in mice
title Oocyte-specific Wee1-like protein kinase 2 is dispensable for fertility in mice
title_full Oocyte-specific Wee1-like protein kinase 2 is dispensable for fertility in mice
title_fullStr Oocyte-specific Wee1-like protein kinase 2 is dispensable for fertility in mice
title_full_unstemmed Oocyte-specific Wee1-like protein kinase 2 is dispensable for fertility in mice
title_short Oocyte-specific Wee1-like protein kinase 2 is dispensable for fertility in mice
title_sort oocyte-specific wee1-like protein kinase 2 is dispensable for fertility in mice
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10393137/
https://www.ncbi.nlm.nih.gov/pubmed/37527245
http://dx.doi.org/10.1371/journal.pone.0289083
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