{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T04:33:36Z","timestamp":1772166816670,"version":"3.50.1"},"reference-count":66,"publisher":"The Endocrine Society","issue":"12","license":[{"start":{"date-parts":[[2022,10,1]],"date-time":"2022-10-01T00:00:00Z","timestamp":1664582400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HL127673"],"award-info":[{"award-number":["HL127673"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HL084207"],"award-info":[{"award-number":["HL084207"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,10,23]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Estrogen receptor alpha (ER\u03b1)\u2013mediated estrogen signaling plays a pivotal role in both reproductive and nonreproductive functions. Transcriptional regulation of the ER\u03b1 gene is highly complex, with multiple transcript variants being differentially produced across the tissues. However, tissue-specific variation and physiological specificity of the ER\u03b1 variants are not yet fully understood. In an attempt to generate a Cre-dependently restorable ER\u03b1-null mouse for functional genetic studies, we unexpectedly produced ER\u03b1 hypomorphic mice with biased downregulation of a previously unappreciated long ER\u03b1 isoform that is enriched in the female reproductive organs (uterus and ovaries) and the pituitary but minimally expressed in the brain. Female homozygous mutant mice were capable of pregnancy but displayed irregular estrus cycle and rarely kept newborn pups alive. No significant morphological and pathological changes in reproductive system or disruption of body weight homeostasis were seen in female homozygous mutant mice. Collectively, our results define a tissue-specific enriched long ER\u03b1 isoform and its preferential role in female reproductive function rather than body weight homeostasis.<\/jats:p>","DOI":"10.1210\/endocr\/bqac160","type":"journal-article","created":{"date-parts":[[2022,10,1]],"date-time":"2022-10-01T06:47:55Z","timestamp":1664606875000},"source":"Crossref","is-referenced-by-count":3,"title":["Hypomorphism of a Novel Long ER\u03b1 Isoform Causes Severe Reproductive Dysfunctions in Female Mice"],"prefix":"10.1210","volume":"163","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6464-4401","authenticated-orcid":false,"given":"Kenji","family":"Saito","sequence":"first","affiliation":[{"name":"Department of Neuroscience and Pharmacology, University of Iowa Carver College of Medicine , Iowa City, IA 52241 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacob E","family":"Dickey","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Pharmacology, University of Iowa Carver College of Medicine , Iowa City, IA 52241 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samuel R","family":"Rodeghiero","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Pharmacology, University of Iowa Carver College of Medicine , Iowa City, IA 52241 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brandon A","family":"Toth","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Pharmacology, University of Iowa Carver College of Medicine , Iowa City, IA 52241 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew J","family":"Kelly","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Pharmacology, University of Iowa Carver College of Medicine , Iowa City, IA 52241 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yue","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Pharmacology, University of Iowa Carver College of Medicine , Iowa City, IA 52241 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Uday","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Pharmacology, University of Iowa Carver College of Medicine , Iowa City, IA 52241 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guorui","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Pharmacology, University of Iowa Carver College of Medicine , Iowa City, IA 52241 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingwei","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Pharmacology, University of Iowa Carver College of Medicine , Iowa City, IA 52241 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8627-8534","authenticated-orcid":false,"given":"Huxing","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Pharmacology, University of Iowa Carver College of Medicine , Iowa City, IA 52241 , USA"},{"name":"Iowa Neuroscience Institute, University of Iowa Carver College of Medicine , Iowa City, IA 52241 , USA"},{"name":"F.O.E. 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