TY - JOUR
T1 - Generation and characterization of a complete null estrogen receptor α mouse using Cre/LoxP technology
AU - Chen, Ming
AU - Wolfe, Andrew
AU - Wang, Xi
AU - Chang, Chawnshang
AU - Yeh, Shuyuan
AU - Radovick, Sally
N1 - Funding Information:
Acknowledgments This work was partly supported by NIH grant DK60912. This research was also supported in part by NICHD/NIH through cooperative agreement (U54 HD 933067, the Baltimore-Chicago Center for Reproductive Research) as part of the Specialized Cooperative Centers Program in Reproduction and Infertility Research (SCCPIR). The technical assistance of Yayoi Shibusawa is gratefully acknowledged. We also thank Karen Wolf and Susan R. Schoen for assisting in manuscript preparation.
PY - 2009
Y1 - 2009
N2 - Conventional estrogen receptor α knockout (neo-ERαKO, neo-ERα-/-) mice contain a truncated and chimeric ERα fusion protein that retains 35% estrogen-dependent transactivation activity, and therefore the in vivo ERα function is difficult to study thoroughly. Furthermore, these neo-ERα-/- mice cannot be used for tissue and temporal specific ERα deletion. Therefore, there is a clear need to establish a floxed ERα mouse line that can knockout ERα specifically and completely in each selected cell type. Here we generated floxed ERα mice using a self-excising ACN (tACE-Cre/Neo) cassette. Mating the floxed ERα mice with ACTB-Cre mice produces a deletion of the floxed allele disrupting the reading frame of the ERα transcript so that no ERα protein is detected in the ACTB-Cre/ERα-/- mice. Expression of ERα target genes, such as G-6-PD and lactoferrin, is diminished by over 90% in the ACTB-Cre/ERα-/- uterus, but not in the neo-ERα-/- uterus. Furthermore, we also validated that ACTB-Cre/ERα-/- 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 ERα mouse is a reliable mouse model for future studies of ERα roles in vivo in the selective estrogen target tissues. The complete knockout of ERα in the ACTB-Cre/ERα-/- mice will also provide an improved mouse model to study the role of ERα in vivo.
AB - Conventional estrogen receptor α knockout (neo-ERαKO, neo-ERα-/-) mice contain a truncated and chimeric ERα fusion protein that retains 35% estrogen-dependent transactivation activity, and therefore the in vivo ERα function is difficult to study thoroughly. Furthermore, these neo-ERα-/- mice cannot be used for tissue and temporal specific ERα deletion. Therefore, there is a clear need to establish a floxed ERα mouse line that can knockout ERα specifically and completely in each selected cell type. Here we generated floxed ERα mice using a self-excising ACN (tACE-Cre/Neo) cassette. Mating the floxed ERα mice with ACTB-Cre mice produces a deletion of the floxed allele disrupting the reading frame of the ERα transcript so that no ERα protein is detected in the ACTB-Cre/ERα-/- mice. Expression of ERα target genes, such as G-6-PD and lactoferrin, is diminished by over 90% in the ACTB-Cre/ERα-/- uterus, but not in the neo-ERα-/- uterus. Furthermore, we also validated that ACTB-Cre/ERα-/- 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 ERα mouse is a reliable mouse model for future studies of ERα roles in vivo in the selective estrogen target tissues. The complete knockout of ERα in the ACTB-Cre/ERα-/- mice will also provide an improved mouse model to study the role of ERα in vivo.
KW - Estrogen receptor α
KW - Female reproduction
KW - Transgenic animal
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U2 - 10.1007/s11010-008-9928-9
DO - 10.1007/s11010-008-9928-9
M3 - Article
C2 - 18953638
AN - SCOPUS:58249131022
SN - 0300-8177
VL - 321
SP - 145
EP - 153
JO - Molecular and Cellular Biochemistry
JF - Molecular and Cellular Biochemistry
IS - 1-2
ER -