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PCOS etiology remains poorly understood, although the hypothalamus is suspected to play a central role in many cases. Human genetic studies have also shown an association with the transcription factor\u2010coding gene\n                    <jats:italic>GATA4<\/jats:italic>\n                    , but without providing a functional link. Here, we show that adult\n                    <jats:italic>Greywick<\/jats:italic>\n                    female mice may bridge this gap. These mice phenocopy PCOS with partial penetrance, due to the serendipitous insertion of a\n                    <jats:italic>Gata4<\/jats:italic>\n                    promoter\u2010driven transgene in a strong enhancer region. Resulting robust transgene expression in subsets of hypothalamic neurons and glia impairs endogenous\n                    <jats:italic>Gata4<\/jats:italic>\n                    expression, resulting in misexpression of genes linked to the control of fertility and food intake. We also show that this previously overlooked role of GATA4 in the hypothalamus can be replicated by conditional knockout approaches. Overall, this study sheds light not only on PCOS etiology but also on the role played by GATA4 in the central control of reproduction.\n                  <\/jats:p>","DOI":"10.1096\/fj.202401718rr","type":"journal-article","created":{"date-parts":[[2025,6,14]],"date-time":"2025-06-14T05:09:56Z","timestamp":1749877796000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Brain\u2010Specific\n                    <i>Gata4<\/i>\n                    Downregulation in\n                    <i>Greywick<\/i>\n                    Female Mice Models the Metabolic Subtype of Polycystic Ovary Syndrome"],"prefix":"10.1096","volume":"39","author":[{"given":"Sherin A.","family":"Nawaito","sequence":"first","affiliation":[{"name":"Molecular Genetics of Development Laboratory, Department of Biological Sciences Universit\u00e9 du Qu\u00e9bec \u00e0 Montr\u00e9al  Montreal Canada"},{"name":"Centre d'Excellence en Recherche sur les 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