Dataset Information

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

ABSTRACT: In 1998, an estrogen receptor ? (ER?) 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 ER? mutant mouse was generated by deleting ER? 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 ER?. In the present study, we created an ER? exon 3-deleted mouse (ER?-?ex3) 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 ER? protein was expressed in nuclei of prostate epithelial cells. Using two different anti-ER? antibodies, we showed that an in-frame ligand binding domain and C terminus were present in the ER?-?ex3 protein. Moreover, with nuclear extracts from ER?-?ex3 prostates, there was an ER?-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 ER?-?ex3 mouse. We conclude that very little of ER? transcriptional activity depends on binding to classical estrogen response elements (EREs).

SUBMITTER: Maneix L

PROVIDER: S-EPMC4413313 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Maneix Laure L Antonson Per P Humire Patricia P Rochel-Maia Sabrina S Castañeda Jessica J Omoto Yoko Y Kim Hyun-Jin HJ Warner Margaret M Gustafsson Jan-Åke JÅ

Proceedings of the National Academy of Sciences of the United States of America 20150406 16

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 ...[more]

PMID: 25848008

Similar Datasets

Project description:Osteoporosis (OP) is distinguished by a reduction in bone mass and degradation of bone micro-structure, frequently resulting in fractures. As the geriatric demographic expands, the incidence of affected individuals progressively rises, thereby exerting a significant impact on the quality of life experienced by individuals. The flavonoid compound hesperidin has been subject to investigation regarding its effects on skeletal health, albeit the precise mechanisms through which it operates remain ambiguous. This study utilized network pharmacology to predict the core targets and signaling pathways implicated in the anti-OP properties of hesperidin. Molecular docking and molecular dynamics simulations were employed to confirm the stability of the interaction between hesperidin and the core targets. The effects of hesperidin on osteoblastic cells MC3T3-E1 were assessed using MTT, ELISA, alkaline phosphatase assay, and RT-qPCR techniques. Furthermore, in vivo experiments were conducted to determine the potential protective effects of hesperidin on zebrafish bone formation and oxidative stress response. The results demonstrate that network pharmacology has identified 10 key target points, significantly enriched in the estrogen signaling pathway. Hesperidin exhibits notable promotion of MC3T3-E1 cell proliferation and significantly enhances ALP activity. ELISA measurements indicate an elevation in NO levels and a reduction in IL-6 and TNF-α. Moreover, RT-qPCR analysis consistently reveals that hesperidin significantly modulates the mRNA levels of ESR1, SRC, AKT1, and NOS3 in MC3T3-E1 cells. Hesperidin promotes osteogenesis and reduces oxidative stress in zebrafish. Additionally, we validate the stable and tight binding of hesperidin with ESR1, SRC, AKT1, and NOS3 through molecular dynamics simulations. In conclusion, our comprehensive analysis provides evidence that hesperidin may exert its effects on alleviating OP through the activation of the estrogen signaling pathway via ESR1. This activation leads to the upregulation of SRC, AKT, and eNOS, resulting in an increase in NO levels. Furthermore, hesperidin promotes osteoblast-mediated bone formation and inhibits pro-inflammatory cytokines, thereby alleviating oxidative stress associated with OP.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets