ArticleEndocrinology2014
Generation of Esr1-knockout rats using zinc finger nuclease-mediated genome editing.
Article in Endocrinology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
45 citing papers in PubMed, 63 citations in OpenAlex.
- The persisting presence of absence in female sex development: a critical interdisciplinary reflection.Biology of sex differences · 2026Review
- Methods for Defining the Role of ADAMTS1 in the Ovary.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Neonatal systemic gene therapy restores cardiorespiratory function in a rat model of Pompe disease.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Rat Models of Breast Cancer.Advances in experimental medicine and biology · 2025Review
- Molecular approaches to mammalian uterine receptivity for conceptus implantation.The Journal of reproduction and development · 2024Review
- The role of the aryl hydrocarbon receptor in mediating the effects of mono(2-ethylhexyl) phthalate in mouse ovarian antral follicles†.Biology of reproduction · 2024Article
- Streamlined identification of clinically and functionally relevant genetic regulators of lower-tract urogenital development.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Reproductive function and behaviors: an update on the role of neural estrogen receptors alpha and beta.Frontiers in endocrinology · 2024Review
- Sex Steroid Receptors in Polycystic Ovary Syndrome and Endometriosis: Insights from Laboratory Studies to Clinical Trials.Biomedicines · 2022Review
- Identification of the TSSK4 Alternative Spliceosomes and Analysis of the Function of the TSSK4 Protein in Yak (Animals : an open access journal from MDPI · 2022Article
- Sexual Dimorphism in Kisspeptin Signaling.Cells · 2022Review
- Recent Advances in the Production of Genome-Edited Rats.International journal of molecular sciences · 2022Review
- Endocrine disorders and fertility and pregnancy: An update.Frontiers in endocrinology · 2022Review
- DOT1L Mediated Gene Repression in Extensively Self-Renewing Erythroblasts.Frontiers in genetics · 2022Article
- ERβ Regulation of Gonadotropin Responses during Folliculogenesis.International journal of molecular sciences · 2021Review
- Kisspeptin Neurons and Estrogen-Estrogen Receptor α Signaling: Unraveling the Mystery of Steroid Feedback System Regulating Mammalian Reproduction.International journal of molecular sciences · 2021Review
- ERβ regulated ovarian kisspeptin plays an important role in oocyte maturation.Molecular and cellular endocrinology · 2021Article
- Estrogen Receptors in Polycystic Ovary Syndrome.Cells · 2021Review
- Mini-Review Regarding the Applicability of Genome Editing Techniques Developed for Studying Infertility.Diagnostics (Basel, Switzerland) · 2021Review
- Disease gene discovery in male infertility: past, present and future.Human genetics · 2021Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Estrogens play pivotal roles in development and function of many organ systems, including the reproductive system. We have generated estrogen receptor 1 (Esr1)-knockout rats using zinc finger nuclease (ZFN) genome targeting. mRNAs encoding ZFNs targeted to exon 3 of Esr1 were microinjected into single-cell rat embryos and transferred to pseudopregnant recipients. Of 17 live births, 5 had biallelic and 1 had monoallelic Esr1 mutations. A founder with monoallelic mutations was backcrossed to a wild-type rat. Offspring possessed only wild-type Esr1 alleles or wild-type alleles and Esr1 alleles containing either 482 bp (Δ482) or 223 bp (Δ223) deletions, indicating mosaicism in the founder. These heterozygous mutants were bred for colony expansion, generation of homozygous mutants, and phenotypic characterization. The Δ482 Esr1 allele yielded altered transcript processing, including the absence of exon 3, aberrant splicing of exon 2 and 4, and a frameshift that generated premature stop codons located immediately after the codon for Thr157. ESR1 protein was not detected in homozygous Δ482 mutant uteri. ESR1 disruption affected sexually dimorphic postnatal growth patterns and serum levels of gonadotropins and sex steroid hormones. Both male and female Esr1-null rats were infertile. Esr1-null males had small testes with distended and dysplastic seminiferous tubules, whereas Esr1-null females possessed large polycystic ovaries, thread-like uteri, and poorly developed mammary glands. In addition, uteri of Esr1-null rats did not effectively respond to 17β-estradiol treatment, further demonstrating that the Δ482 Esr1 mutation created a null allele. This rat model provides a new experimental tool for investigating the pathophysiology of estrogen action.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.