{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T12:29:49Z","timestamp":1764678589017,"version":"3.46.0"},"reference-count":0,"publisher":"EHU Press","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Dev. Biol."],"published-print":{"date-parts":[[2024]]},"abstract":"<jats:p>\n                    Wnt4 signaling is critical for mammalian female sex determination, in female reproductive organ development, in follicular and oocyte maturation, and in steroid hormone production. When Wnt4 function is impaired, female embryos undergo partial female to male sex-reversal. This phenotype is associated with the expression of a set of somatic genes that are typical for the male differentiation pathways such as those of the Leydig cells. Given the roles of the 3`untranslated region\n                    <jats:italic\/>\n                    (\n                    <jats:italic>3`UTR<\/jats:italic>\n                    ) in control of gene expression, we addressed whether a knock-in of a stop cassette to 3`END of the\n                    <jats:italic>Wnt4<\/jats:italic>\n                    gene would impact female reproductive system development or function. The\n                    <jats:italic>\n                      3`UTR\n                      <jats:sup>stop<\/jats:sup>\n                    <\/jats:italic>\n                    cassette indeed affected\n                    <jats:italic>Wnt4<\/jats:italic>\n                    gene expression\n                    <jats:italic>in vivo<\/jats:italic>\n                    so that the respective mRNA was upregulated in the ovaries of a three month-old female. The homozygous\n                    <jats:italic>\n                      Wnt4 3`UTR\n                      <jats:sup>stop<\/jats:sup>\n                    <\/jats:italic>\n                    mice were noted to be leaner than their wild type (WT) littermate controls. Analysis of the ovarian follicular count at the age of three months revealed increased pre-antral but reduced ovarian corpus luteum follicular counts. Furthermore, two out of five of the homozygous female\n                    <jats:italic>\n                      Wnt4 3`UTR\n                      <jats:sup>stop<\/jats:sup>\n                    <\/jats:italic>\n                    mice had ovarian cysts, not noted in WT controls. RT-qPCR and\n                    <jats:italic>in situ<\/jats:italic>\n                    hybridization analysis depicted changes in the expression of a panel of genes which encode enzymes that mediate the synthesis of female steroid hormones or their receptors due to the\n                    <jats:italic>\n                      Wnt4 3`UTR\n                      <jats:sup>stop<\/jats:sup>\n                    <\/jats:italic>\n                    knock-in. Thus, female mice which had the homozygous construct exhibited elevated ovarian\n                    <jats:italic>Wnt4<\/jats:italic>\n                    mRNA expression and the corresponding knock-in was associated with changes in ovarian development and folliculogenesis. Our data reinforce the conclusion that deregulated\n                    <jats:italic>Wnt4<\/jats:italic>\n                    expression impacts female sex organogenesis, ovary development and function, and that the\n                    <jats:italic>\n                      Wnt4 3`UTR\n                      <jats:sup>stop<\/jats:sup>\n                    <\/jats:italic>\n                    knock-in mouse provides a model to explore in more detail the roles of Wnt4 signaling in the process.\n                  <\/jats:p>","DOI":"10.1387\/ijdb.230211na","type":"journal-article","created":{"date-parts":[[2024,11,4]],"date-time":"2024-11-04T07:42:32Z","timestamp":1730706152000},"page":"241-249","source":"Crossref","is-referenced-by-count":0,"title":["Knock-in of a\n                    <i>3\u2019 UTR<\/i>\n                    Stop Cassette into the\n                    <i>Wnt4<\/i>\n                    locus increases mRNA expression and leads to ovarian cyst formation"],"prefix":"10.1387","volume":"68","author":[{"given":"Nsrein","family":"Ali","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qi","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Renata","family":"Prunskaite-Hyyryl\u00e4inen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingdong","family":"Shan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seppo J.","family":"Vainio","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"352","container-title":["The International Journal of Developmental Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ijdb.ehu.eus\/article\/pdf\/230211na","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ijdb.ehu.eus\/article\/230211na","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,27]],"date-time":"2025-02-27T08:05:05Z","timestamp":1740643505000},"score":1,"resource":{"primary":{"URL":"https:\/\/ijdb.ehu.eus\/article\/230211na"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024]]},"references-count":0,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2024]]}},"alternative-id":["230211na"],"URL":"https:\/\/doi.org\/10.1387\/ijdb.230211na","relation":{},"ISSN":["0214-6282","1696-3547"],"issn-type":[{"type":"print","value":"0214-6282"},{"type":"electronic","value":"1696-3547"}],"subject":[],"published":{"date-parts":[[2024]]}}}