Estrogen receptor β exon 3-deleted mouse: The importance of non-ERE pathways in ERβ signaling

Laure Maneix, Per Antonson, Patricia Humire, Sabrina Rochel-Maia, Jessica Castañeda, Yoko Omoto, Hyun Jin Kim, Margaret Warner, Jan Åke Gustafsson

Research output: Contribution to journalArticle

21 Scopus citations

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 ERβexon 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).

Original languageEnglish (US)
Pages (from-to)5135-5140
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume112
Issue number16
DOIs
StatePublished - Apr 21 2015

Keywords

  • AP-1
  • Mouse model
  • Nuclear receptors
  • Targeted disruption
  • Ventral prostate

ASJC Scopus subject areas

  • General

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