Generation and characterization of a complete null estrogen receptor alpha mouse using Cre/LoxP technology.

Published

Journal Article

Conventional estrogen receptor alpha knockout (neo-ERalphaKO, neo-ERalpha(-/-)) mice contain a truncated and chimeric ERalpha fusion protein that retains 35% estrogen-dependent transactivation activity, and therefore the in vivo ERalpha function is difficult to study thoroughly. Furthermore, these neo-ERalpha(-/-) mice cannot be used for tissue and temporal specific ERalpha deletion. Therefore, there is a clear need to establish a floxed ERalpha mouse line that can knockout ERalpha specifically and completely in each selected cell type. Here we generated floxed ERalpha mice using a self-excising ACN (tACE-Cre/Neo) cassette. Mating the floxed ERalpha mice with ACTB-Cre mice produces a deletion of the floxed allele disrupting the reading frame of the ERalpha transcript so that no ERalpha protein is detected in the ACTB-Cre/ERalpha(-/-) mice. Expression of ERalpha target genes, such as G-6-PD and lactoferrin, is diminished by over 90% in the ACTB-Cre/ERalpha(-/-) uterus, but not in the neo-ERalpha(-/-) uterus. Furthermore, we also validated that ACTB-Cre/ERalpha(-/-) females have a hypoplastic internal genital tract, polycystic ovaries with hemorrhagic follicles, infertility, and higher body weight. Together, our data clearly demonstrate that the newly established floxed ERalpha mouse is a reliable mouse model for future studies of ERalpha roles in vivo in the selective estrogen target tissues. The complete knockout of ERalpha in the ACTB-Cre/ERalpha(-/-) mice will also provide an improved mouse model to study the role of ERalpha in vivo.

Full Text

Duke Authors

Cited Authors

  • Chen, M; Wolfe, A; Wang, X; Chang, C; Yeh, S; Radovick, S

Published Date

  • January 2009

Published In

Volume / Issue

  • 321 / 1-2

Start / End Page

  • 145 - 153

PubMed ID

  • 18953638

Pubmed Central ID

  • 18953638

Electronic International Standard Serial Number (EISSN)

  • 1573-4919

Digital Object Identifier (DOI)

  • 10.1007/s11010-008-9928-9

Language

  • eng

Conference Location

  • Netherlands