| First Author | Hewitt SC | Year | 2010 |
| Journal | FASEB J | Volume | 24 |
| Issue | 12 | Pages | 4660-7 |
| PubMed ID | 20667977 | Mgi Jnum | J:191182 |
| Mgi Id | MGI:5461142 | Doi | 10.1096/fj.10-163428 |
| Citation | Hewitt SC, et al. (2010) Biological and biochemical consequences of global deletion of exon 3 from the ER alpha gene. FASEB J 24(12):4660-7 |
| abstractText | To address issues resulting from alpha estrogen receptor-knockout (alphaERKO) residual N-terminal truncated estrogen receptor alpha, and to allow tissue-selective deletion of ERalpha, we generated loxP-flanked exon 3 mice. Initial characterization of global sox2 cre-derived exon 3-deleted Ex3alphaERKO mice indicated no ERalpha protein in uterine tissue and recapitulation of previously described female phenotypes, confirming successful ablation of ERalpha. Body weights of Ex3alphaERKO female mice were 1.4-fold higher than wild-tupe (WT) females and comparable to WT males. Microarray indicated the Ex3alphaERKO uterus is free of residual estrogen responses. RT-PCR showed Nr4a1 is increased 41-fold by estrogen in WT and 7.4-fold in alphaERKO, and not increased in Ex3alphaERKO. Nr4a1, Cdkn1a, and c-fos transcripts were evaluated in WT and Ex3alphaERKO mice following estrogen, IGF1, or EGF injections. All 3 were increased by all treatments in WT. None were increased by estrogen in Ex3alphaERKO. Nr4a1 increased 24.5- and 14.7-fold, Cdkn1a increased 14.2- and 12.3-fold, and c-fos increased 20.9-fold and 16.2-fold after IGF1 and EGF treatments, respectively, in the Ex3alphaERKO mice, confirming that growth factor regulation is independent of ERalpha. Our Ex3alpha ERalpha model will be useful in studies of complete or selective ablation of ERalpha in target tissues. |
