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Biological and biochemical consequences of global deletion of exon 3 from the ERα gene
Open accessAbstract
To address issues resulting from α estrogen receptor-knockout (αERKO) residual N-terminal truncated estrogen receptor α, and to allow tissue-selective deletion of ERα, we generated loxP-flanked exon 3 mice. Initial characterization of global sox2 cre-derived exon 3-deleted Ex3αERKO mice indicated no ERα protein in uterine tissue and recapitulation of previously described female phenotypes, confirming successful ablation of ERα. Body weights of Ex3αERKO female mice were 1.4-fold higher than wild-tupe (WT) females and comparable to WT males. Microarray indicated the Ex3αERKO uterus is free of residual estrogen responses. RT-PCR showed Nr4a1 is increased 41-fold by estrogen in WT and 7.4-fold in αERKO, and not increased in Ex3αERKO. Nr4a1, Cdkn1a, and c-fos transcripts were evaluated in WT and Ex3αERKO mice following estrogen, IGF1, or EGF injections. All 3 were increased by all treatments in WT. None were increased by estrogen in Ex3αERKO. 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 Ex3αERKO mice, confirming that growth factor regulation is independent of ERα. Our Ex3α ERα model will be useful in studies of complete or selective ablation of ERα in target tissues.
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Cites
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Self-citationVanderschueren, D., Vandenput, L., Boonen, S., Lindberg, M. K., Bouillon, R., & Ohlsson, C. (2004) · Endocrine Reviews · doi:10.1210/er.2003-0003 · Cited by 717
Obesity and Disturbed Lipoprotein Profile in Estrogen Receptor-α-Deficient Male Mice
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Cited by
Hamilton, K. J., Hewitt, S. C., Arao, Y., & Korach, K. S. (2017) · Current Topics in Developmental Biology · doi:10.1016/bs.ctdb.2016.12.005 · Cited by 336
Self-citationSex Steroid Actions in Male Bone
Vanderschueren, D., Laurent, M. R., Claessens, F., Gielen, E., Lagerquist, M. K., Vandenput, L., Börjesson, A. E., & Ohlsson, C. (2014) · Endocrine Reviews · doi:10.1210/er.2014-1024 · Cited by 327
Ribas, V., Drew, B. G., Zhou, Z., Phun, J., Kalajian, N. Y., Soleymani, T., Daraei, P., Widjaja, K., Wanagat, J., de Aguiar Vallim, T. Q., et al. (2016) · Science Translational Medicine · doi:10.1126/scitranslmed.aad3815 · Cited by 259
Self-citationDual suppression of estrogenic and inflammatory activities for targeting of endometriosis
Zhao, Y., Gong, P., Chen, Y., Nwachukwu, J. C., Srinivasan, S., Ko, C., Bagchi, M. K., Taylor, R. N., Korach, K. S., Nettles, K. W., et al. (2015) · Science Translational Medicine · doi:10.1126/scitranslmed.3010626 · Cited by 170
Self-citationTorres, M. J., Kew, K. A., Ryan, T. E., Pennington, E. R., Lin, C.-T., Buddo, K. A., Fix, A. M., Smith, C. A., Gilliam, L. A., Karvinen, S., et al. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2017.10.003 · Cited by 170
Metadata
- Authors
- Hewitt, S. C., Kissling, G. E., Fieselman, K. E., Jayes, F. L., Gerrish, K. E., & Korach, K. S.
- Venue
- The FASEB Journal
- Publisher
- Wiley
- Published
- 2010-12
- Volume
- 24
- Issue
- 12
- Pages
- 4660-4667
- ISSN
- 0892-6638 (ISSN-L)
- 1530-6860
- OpenAlex
- W2098316774
- Cited by
- 161
- References
- 3
- FWCI
- 4.36
- Type
- journal article
- Language
- en
- Open access
- green
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- Hewitt, S. C., Kissling, G. E., Fieselman, K. E., Jayes, F. L., Gerrish, K. E., & Korach, K. S. (2010). Biological and biochemical consequences of global deletion of exon 3 from the ERα gene. The FASEB Journal. https://doi.org/10.1096/fj.10-163428
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