Hypomorphism of a novel long ERα isoform causes severe reproductive dysfunctions in female mice

Kenji Saito; Jacob E Dickey; Samuel R Rodeghiero; Brandon A Toth; Matthew J Kelly; Yue Deng; Uday Singh; Guorui Deng; Jingwei Jiang; Huxing Cui

doi:10.1210/endocr/bqac160

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Hypomorphism of a novel long ERα isoform causes severe reproductive dysfunctions in female mice

Journal article

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Hypomorphism of a novel long ERα isoform causes severe reproductive dysfunctions in female mice

Kenji Saito, Jacob E Dickey, Samuel R Rodeghiero, Brandon A Toth, Matthew J Kelly, Yue Deng, Uday Singh, Guorui Deng, Jingwei Jiang and Huxing Cui

Endocrinology (Philadelphia), Vol.163(12), bqac160

10/01/2022

DOI: 10.1210/endocr/bqac160

PMCID: PMC10233398

PMID: 36181426

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Abstract

Estrogen receptor alpha (ERα)-mediated estrogen signaling plays a pivotal role in both reproductive and nonreproductive functions. Transcriptional regulation of the ERα gene is highly complex, with multiple transcript variants being differentially produced across the tissues. However, tissue-specific variation and physiological specificity of the ERα variants are not yet fully understood. In an attempt to generate a Cre-dependently restorable ERα-null mouse for functional genetic studies, we unexpectedly produced ERα hypomorphic mice with biased downregulation of a previously unappreciated long ERα 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 ERα isoform and its preferential role in female reproductive function rather than body weight homeostasis.

Details

Title: Subtitle: Hypomorphism of a novel long ERα isoform causes severe reproductive dysfunctions in female mice
Creators: Kenji Saito - Roy J. and Lucille A. Carver College of Medicine
Jacob E Dickey - Roy J. and Lucille A. Carver College of Medicine
Samuel R Rodeghiero - Roy J. and Lucille A. Carver College of Medicine
Brandon A Toth - Roy J. and Lucille A. Carver College of Medicine
Matthew J Kelly - Roy J. and Lucille A. Carver College of Medicine
Yue Deng - Roy J. and Lucille A. Carver College of Medicine
Uday Singh - Roy J. and Lucille A. Carver College of Medicine
Guorui Deng - Roy J. and Lucille A. Carver College of Medicine
Jingwei Jiang - Roy J. and Lucille A. Carver College of Medicine
Huxing Cui - Roy J. and Lucille A. Carver College of Medicine
Resource Type: Journal article
Publication Details: Endocrinology (Philadelphia), Vol.163(12), bqac160
DOI: 10.1210/endocr/bqac160
PMID: 36181426
PMCID: PMC10233398
NLM abbreviation: Endocrinology
ISSN: 0013-7227
eISSN: 1945-7170
Grant note: DOI: 10.13039/100000002, name: National Institutes of Health, award: HL127673, HL084207
Language: English
Date published: 10/01/2022
Academic Unit: Iowa Neuroscience Institute; Fraternal Order of Eagles Diabetes Research Center; Neuroscience and Pharmacology
Record Identifier: 9984303288202771

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