Complete knockout of estrogen receptor alpha is not directly protective in murine lupus
Copyright © 2017 Elsevier Inc. All rights reserved.
| Veröffentlicht in: | Clinical immunology (Orlando, Fla.). - 1999. - 183(2017) vom: 29. Okt., Seite 132-141 |
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| 1. Verfasser: | |
| Weitere Verfasser: | , , , |
| Format: | Online-Aufsatz |
| Sprache: | English |
| Veröffentlicht: |
2017
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| Zugriff auf das übergeordnete Werk: | Clinical immunology (Orlando, Fla.) |
| Schlagworte: | Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S. Autoantibody Estrogen Estrogen receptor alpha Lupus Testosterone Antibodies, Antinuclear Autoantibodies mehr... |
| Zusammenfassung: | Copyright © 2017 Elsevier Inc. All rights reserved. Systemic lupus erythematosus (SLE) is a chronic and potentially severe autoimmune disease that disproportionately affects women. Despite a known role for hormonal factors impacting autoimmunity and disease pathogenesis, the specific mechanisms of action remain poorly understood. Our laboratory previously backcrossed "estrogen receptor alpha knockout (ERαKO)" mice onto the NZM2410 lupus prone background to generate NZM/ERαKO mice. This original ERαKO mouse, developed in the mid-1990s and utilized in hundreds of published studies, is not in fact ERα null. They express an N-terminally truncated ERα, and are considered a functional KO. They have physiologic deficiencies including infertility due to disruption of a critical activation domain (AF-1) at the N terminus of ERα, required for most classic estrogen (E2) actions. We demonstrated that female NZM/ERαKO mice had significantly less renal disease and significantly prolonged survival compared to WT littermates despite similar serum levels of autoantibodies and glomerular immune complex deposition. Herein, we present results of experiments using a lupus prone true ERα-/- mice (deletional KO mice on the NZM2410 background), surprisingly finding that these animals were not protected if they were ovariectomized, suggesting that another hormonal component confers protection, possibly testosterone, rather than the absence of the full-length ERα |
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| Beschreibung: | Date Completed 21.11.2017 Date Revised 07.12.2018 published: Print-Electronic Citation Status MEDLINE |
| ISSN: | 1521-7035 |
| DOI: | 10.1016/j.clim.2017.08.010 |