Hypomorphism of a Novel Long ERα Isoform Causes Severe Reproductive Dysfunctions in Female Mice.
Endocrinology
; 163(12)2022 10 23.
Article
em En
| MEDLINE
| ID: mdl-36181426
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.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Receptor alfa de Estrogênio
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Estrogênios
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Fenômenos Reprodutivos Fisiológicos
Tipo de estudo:
Etiology_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article