{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T18:28:29Z","timestamp":1766168909572,"version":"3.48.0"},"reference-count":53,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T00:00:00Z","timestamp":1766102400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Eunice Kennedy Shriver National Institute of Child Health & Human Development of the National Institute of Health","award":["R01 HD103617"],"award-info":[{"award-number":["R01 HD103617"]}]},{"name":"Eunice Kennedy Shriver National Institute of Child Health & Human Development of the National Institute of Health","award":["T32HD087166"],"award-info":[{"award-number":["T32HD087166"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    Chromatin remodeling plays an integral part in endometrial homeostasis through its roles in the maintenance of cell identity, epithelial integrity, and prevention of endometrial disease. Chromodomain-helicase-DNA-binding protein 4 (CHD4) is a chromatin remodeling protein and member of the NuRD complex, which predominantly represses transcription.\n                    <jats:italic>CHD4<\/jats:italic>\n                    is mutated in endometrial carcinoma, with most mutations resulting in loss of function.\n                    <jats:italic>CHD4<\/jats:italic>\n                    has been identified as a tumor suppressor and regulator of stemness in human endometrial carcinoma cell lines, but little is known about the tissue-specific roles of\n                    <jats:italic>CHD4<\/jats:italic>\n                    in the endometrial epithelia\n                    <jats:italic>in vivo.<\/jats:italic>\n                    We generated a conditional\n                    <jats:italic>Chd4<\/jats:italic>\n                    floxed allele and combined it with\n                    <jats:italic>BAC-Sprr2f-Cre<\/jats:italic>\n                    to drive CHD4 loss in the endometrial epithelium. Consistent with previous reports,\n                    <jats:italic>BAC-Sprr2f-Cre<\/jats:italic>\n                    shows variegated expression within the endometrial epithelium and lacks expression in the oviducts, ovaries, and kidneys. Loss of CHD4 was confirmed by immunohistochemistry, and the percentage of endometrial epithelial cells with and without CHD4 was quantified. Compared to the glandular epithelium, the extent of CHD4 loss was higher in the luminal epithelium and unaffected by age. Mice with conditional knockout of\n                    <jats:italic>Chd4<\/jats:italic>\n                    had normal endometrial histology. A six-month breeding trial was performed to assess the functional effects of endometrial epithelial CHD4 loss on fertility and found no difference in litter size, average litter size per dam, or pup weight between genotypes. These findings demonstrate that\n                    <jats:italic>Chd4<\/jats:italic>\n                    conditional knockout using\n                    <jats:italic>BAC-Sprr2f-Cre<\/jats:italic>\n                    is not sufficient to alter the structure and function of the endometrial epithelium or drive tumorigenesis. As\n                    <jats:italic>CHD4<\/jats:italic>\n                    is frequently co-mutated with other cancer driver genes such as\n                    <jats:italic>TP53<\/jats:italic>\n                    ,\n                    <jats:italic>PIK3CA<\/jats:italic>\n                    , and\n                    <jats:italic>PTEN<\/jats:italic>\n                    , future mouse modeling efforts emulating patient mutational profiles might provide insight into the role of\n                    <jats:italic>CHD4<\/jats:italic>\n                    in endometrial carcinoma.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0326723","type":"journal-article","created":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T18:24:27Z","timestamp":1766168667000},"page":"e0326723","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Generation and characterization of a mouse model of conditional 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