title: Estrogen receptor β exon 3-deleted mouse: The importance of non-ERE pathways in ERβ signaling.
abstract: In 1998, an estrogen receptor β (ERβ) knockout (KO) mouse was created by interrupting the gene at the DNA binding domain (DBD) with a neocassette. The mutant females were subfertile and there were abnormalities in the brain, prostate, lung, colon, and immune system. In 2008, another ERβ mutant mouse was generated by deleting ERβ exon 3 which encodes the first zinc finger in the DBD. The female mice of this strain were unable to ovulate but were otherwise normal. The differences in the phenotypes of the two KO strains, have led to questions about the physiological function of ERβ. In the present study, we created an ERβ exon 3-deleted mouse (ERβ-Δex3) and confirmed that the only observable defect was anovulation. Despite the two in-frame stop codons introduced by splicing between exons 2 and 4, an ERβ protein was expressed in nuclei of prostate epithelial cells. Using two different anti-ERβ antibodies, we showed that an in-frame ligand binding domain and C terminus were present in the ERβ-Δex3 protein. Moreover, with nuclear extracts from ERβ-Δex3 prostates, there was an ERβ-dependent retardation of migration of activator protein-1 response elements in EMSA. Unlike the original knockout mouse, expression of Ki67, androgen receptor, and Dachshund-1 in prostate epithelium was not altered in the ERβ-Δex3 mouse. We conclude that very little of ERβ transcriptional activity depends on binding to classical estrogen response elements (EREs).
authors.affiliation: Center for Nuclear Receptors and Cell Signaling, Department of Biology and Biochemistry, University of Houston, Houston, TX 77204; and.
authors.forename: Laure
authors.initials: L
authors.lastname: Maneix
authors.affiliation: Center for Biosciences, Department of Biosciences and Nutrition, Karolinska Institutet, Novum, 14186 Stockholm, Sweden.
authors.forename: Per
authors.initials: P
authors.lastname: Antonson
authors.affiliation: Center for Biosciences, Department of Biosciences and Nutrition, Karolinska Institutet, Novum, 14186 Stockholm, Sweden.
authors.forename: Patricia
authors.initials: P
authors.lastname: Humire
authors.affiliation: Center for Nuclear Receptors and Cell Signaling, Department of Biology and Biochemistry, University of Houston, Houston, TX 77204; and.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Rochel-Maia
authors.affiliation: Center for Nuclear Receptors and Cell Signaling, Department of Biology and Biochemistry, University of Houston, Houston, TX 77204; and.
authors.forename: Jessica
authors.initials: J
authors.lastname: Castañeda
authors.affiliation: Center for Biosciences, Department of Biosciences and Nutrition, Karolinska Institutet, Novum, 14186 Stockholm, Sweden.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Omoto
authors.affiliation: Center for Nuclear Receptors and Cell Signaling, Department of Biology and Biochemistry, University of Houston, Houston, TX 77204; and.
authors.forename: Hyun-Jin
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Center for Nuclear Receptors and Cell Signaling, Department of Biology and Biochemistry, University of Houston, Houston, TX 77204; and.
authors.forename: Margaret
authors.initials: M
authors.lastname: Warner
authors.affiliation: Center for Nuclear Receptors and Cell Signaling, Department of Biology and Biochemistry, University of Houston, Houston, TX 77204; and Center for Biosciences, Department of Biosciences and Nutrition, Karolinska Institutet, Novum, 14186 Stockholm, Sweden jgustafsson@uh.edu.
authors.forename: Jan-Åke
authors.initials: JÅ
authors.lastname: Gustafsson
mesh_terms: D000818:Animals; D004247:DNA / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000235:genetics*; D005091:Exons / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation; D018390:Gene Targeting; D008297:Male; D008817:Mice, Mutant Strains; D010053:Ovary / Q000503:physiopathology; D011467:Prostate / Q000378:metabolism / Q000473:pathology; D011485:Protein Binding / Q000235:genetics; D021381:Protein Transport; D011944:Receptors, Androgen / Q000378:metabolism; D015203:Reproducibility of Results; D020218:Response Elements / Q000235:genetics*; D017384:Sequence Deletion / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics*; D018808:Transcription Factor AP-1 / Q000378:metabolism
chemical_list: D047629:Estrogen Receptor beta; D011944:Receptors, Androgen; D018808:Transcription Factor AP-1; D004247:DNA
keywords: AP-1; mouse model; nuclear receptors; targeted disruption; ventral prostate
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