An estrogen receptor alpha activity indicator model in mice.

Estrogen receptor alpha (ERalpha), plays essential roles in the female reproduction. To investigate the dynamic changes in ERalpha activity in vivo, we have developed an ER Alpha Activity Indicator (ERAAI) mouse. This ERAAI mouse harbors both a modified ERalpha Bacterial Artificial Chromosome (BAC) clone and a reporter gene which is regulated specifically by the modified receptor. The ERalpha modification (Gal4-ERalpha) consists replacing the DNA binding domain (DBD) of ERalpha with the DBD of yeast Gal4 transcription factor. This reporter transgene consisting of a humanized renilla Green Fluorescent Protein (hrGFP) sequence controlled by the Upstream Activating Sequences for the Gal4 gene (UAS(G)) was inserted into the modified ERalpha BAC clone. Expression of Gal4-ERalpha and hrGFP reliably recapitulates endogenous ERalpha expression and activity in the estrogen target tissues in response to estrogen stimulation. Therefore, the ERAAI mouse represents a novel animal model to investigate dynamic ERalpha activity in vivo.