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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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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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.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0289083</identifier><identifier>PMID: 37527245</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Analysis ; Animal models ; Animals ; Biology and Life Sciences ; Cell cycle ; Cell Cycle Proteins - genetics ; Cell Cycle Proteins - metabolism ; Contraception ; Contraceptives ; CRISPR ; Cyclin-dependent kinases ; Deletion ; Embryos ; Engineering and Technology ; Exons ; Fecundity ; Female ; Females ; Fertility ; Fertility - genetics ; Frameshift mutation ; Gametocytes ; Health aspects ; Histology ; Humans ; In vitro fertilization ; Infertility ; Kinases ; Litter size ; Medicine ; Medicine and Health Sciences ; Meiosis ; Mice ; Mutation ; Oocytes ; Oocytes - metabolism ; Ovaries ; Ovulation ; Phenotypes ; Phosphorylation ; Prophase ; Protein interaction ; Protein Kinases - metabolism ; Protein-protein interactions ; Protein-tyrosine kinase ; Protein-Tyrosine Kinases - genetics ; Protein-Tyrosine Kinases - metabolism ; Proteins ; Research and Analysis Methods ; Statistical significance ; Surgery ; Tyrosine</subject><ispartof>PloS one, 2023-08, Vol.18 (8), p.e0289083</ispartof><rights>Copyright: © 2023 Nozawa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</rights><rights>COPYRIGHT 2023 Public Library of Science</rights><rights>2023 Nozawa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2023 Nozawa et al 2023 Nozawa et al</rights><rights>2023 Nozawa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c642t-aec705521cc97161693ac0b1cac1d894569211341f696303e22b7b61c94986ea3</cites><orcidid>0000-0001-5660-6392 ; 0000-0001-9207-9374 ; 0000-0002-1445-8632 ; 0000-0001-9859-6217</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10393137/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10393137/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2095,2914,23846,27903,27904,53769,53771,79346,79347</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37527245$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Cui, Wei</contributor><creatorcontrib>Nozawa, Kaori</creatorcontrib><creatorcontrib>Liao, Zian</creatorcontrib><creatorcontrib>Satouh, Yuhkoh</creatorcontrib><creatorcontrib>Geng, Ting</creatorcontrib><creatorcontrib>Ikawa, Masahito</creatorcontrib><creatorcontrib>Monsivais, Diana</creatorcontrib><creatorcontrib>Matzuk, Martin M</creatorcontrib><title>Oocyte-specific Wee1-like protein kinase 2 is dispensable for fertility in mice</title><title>PloS one</title><addtitle>PLoS One</addtitle><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. 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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. 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subjects | Analysis Animal models Animals Biology and Life Sciences Cell cycle Cell Cycle Proteins - genetics Cell Cycle Proteins - metabolism Contraception Contraceptives CRISPR Cyclin-dependent kinases Deletion Embryos Engineering and Technology Exons Fecundity Female Females Fertility Fertility - genetics Frameshift mutation Gametocytes Health aspects Histology Humans In vitro fertilization Infertility Kinases Litter size Medicine Medicine and Health Sciences Meiosis Mice Mutation Oocytes Oocytes - metabolism Ovaries Ovulation Phenotypes Phosphorylation Prophase Protein interaction Protein Kinases - metabolism Protein-protein interactions Protein-tyrosine kinase Protein-Tyrosine Kinases - genetics Protein-Tyrosine Kinases - metabolism Proteins Research and Analysis Methods Statistical significance Surgery Tyrosine |
title | Oocyte-specific Wee1-like protein kinase 2 is dispensable for fertility in mice |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-24T15%3A39%3A14IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Oocyte-specific%20Wee1-like%20protein%20kinase%202%20is%20dispensable%20for%20fertility%20in%20mice&rft.jtitle=PloS%20one&rft.au=Nozawa,%20Kaori&rft.date=2023-08-01&rft.volume=18&rft.issue=8&rft.spage=e0289083&rft.pages=e0289083-&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0289083&rft_dat=%3Cgale_plos_%3EA759254650%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2844636057&rft_id=info:pmid/37527245&rft_galeid=A759254650&rft_doaj_id=oai_doaj_org_article_9c7081c042f6466f8c4619d20bec97a6&rfr_iscdi=true |