| First Author | Saito K | Year | 2022 |
| Journal | Endocrinology | Volume | 163 |
| Issue | 12 | PubMed ID | 36181426 |
| Mgi Jnum | J:333892 | Mgi Id | MGI:7442738 |
| Doi | 10.1210/endocr/bqac160 | Citation | Saito K, et al. (2022) Hypomorphism of a Novel Long ERalpha Isoform Causes Severe Reproductive Dysfunctions in Female Mice. Endocrinology 163(12) |
| abstractText | Estrogen receptor alpha (ERalpha)-mediated estrogen signaling plays a pivotal role in both reproductive and nonreproductive functions. Transcriptional regulation of the ERalpha gene is highly complex, with multiple transcript variants being differentially produced across the tissues. However, tissue-specific variation and physiological specificity of the ERalpha variants are not yet fully understood. In an attempt to generate a Cre-dependently restorable ERalpha-null mouse for functional genetic studies, we unexpectedly produced ERalpha hypomorphic mice with biased downregulation of a previously unappreciated long ERalpha 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 ERalpha isoform and its preferential role in female reproductive function rather than body weight homeostasis. |
