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

First Author  Chen M Year  2009
Journal  Mol Cell Biochem Volume  321
Issue  1-2 Pages  145-53
PubMed ID  18953638 Mgi Jnum  J:147191
Mgi Id  MGI:3839669 Doi  10.1007/s11010-008-9928-9
Citation  Chen M, et al. (2009) Generation and characterization of a complete null estrogen receptor alpha mouse using Cre/LoxP technology. Mol Cell Biochem 321(1-2):145-53
abstractText  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.
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