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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Krust, A. Darblade, B. Rochaix, P. Bayard, F. Korach, K. S. Pendaries, C. Arnal, J. F. Chambon, P. |
| Description | Author Affiliation: Pendaries C ( Institut National de la Santé et de la Recherche Médicale U397 et Laboratoire de Physiologie, Institut Louis Bugnard, Centre Hospitalier Universitaire Rangueil, 31054 Toulouse, France.); |
| Abstract | Two isoforms of estrogen receptor (ER) have been described: ERalpha and ERbeta. The initial gene targeting of ERalpha, consisting in the introduction of a Neo cassette in exon 1 [alphaERKO, hereafter called ERalpha-Neo KO (knockout)], was reported in 1993. More recently, another mouse deficient in ERalpha because of the deletion of exon 2 (ERalphaKO, hereafter called ERalpha-delta2 KO) was generated. In ovariectomized ERalpha-wild-type mice, estradiol (E(2)) increases uterine weight and basal production of endothelial nitric oxide (NO). Both of these effects are abolished in ERalpha-delta2 KO mice. In contrast, we show here that both of these effects of E(2) are partially (uterine weight) or totally (endothelial NO production) preserved in ERalpha-Neo KO. We also confirm the presence of two ERalpha mRNA splice variants in uterus and aorta from ERalpha-Neo KO mice. One of them encodes a chimeric ERalpha protein (ERalpha55), partially deleted in the A/B domain, that was detected in both uterus and aorta by Western blot analysis. The other ERalpha mRNA splice variant codes for an isoform deleted for the A/B domain (ERalpha46), which was detected in uterus of ERalpha-Neo KO, and wild-type mice. This protein isoform was not detected in aorta. The identification of these two N-terminal modified isoforms in uterus, and at least one of them in aorta, probably explains the persistence of the E(2) effects in ERalpha-Neo KO mice. Furthermore, ERalpha-Neo KO mice may help in the elucidation of the specific functions of full-length ERalpha (ERalpha66) and ERalpha46, both shown to be physiologically generated in vivo. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 4 |
| Volume Number | 99 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2002-02-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Estradiol Pharmacology Nitric Oxide Biosynthesis Receptors, Estrogen Genetics Physiology Alternative Splicing Animals Aorta Metabolism Blotting, Western Dose-Response Relationship, Drug Endothelium, Vascular Estrogen Receptor Alpha Exons Hypertrophy Immunohistochemistry Mice Mice, Knockout Models, Genetic Mutagenesis, Insertional Organ Size Protein Isoforms Protein Structure, Tertiary RNA, Messenger Reverse Transcriptase Polymerase Chain Reaction Uterus Drug Effects Pathology Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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