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

نویسندگان

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

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).

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عنوان ژورنال:
  • Proceedings of the National Academy of Sciences of the United States of America

دوره 112 16  شماره 

صفحات  -

تاریخ انتشار 2015