| First Author | Chen L | Year | 2018 |
| Journal | Am J Physiol Renal Physiol | Volume | 314 |
| Issue | 4 | Pages | F572-F583 |
| PubMed ID | 29357435 | Mgi Jnum | J:281293 |
| Mgi Id | MGI:6367914 | Doi | 10.1152/ajprenal.00436.2017 |
| Citation | Chen L, et al. (2018) Highly tamoxifen-inducible principal cell-specific Cre mice with complete fidelity in cell specificity and no leakiness. Am J Physiol Renal Physiol 314(4):F572-F583 |
| abstractText | An ideal inducible system should be cell specific and have absolutely no background recombination without induction (i.e., no leakiness), a high recombination rate after induction, and complete fidelity in cell specificity (i.e., restricted recombination exclusively in cells where the driver gene is expressed). However, such an ideal mouse model remains unavailable for collecting duct research. Here, we report a mouse model that meets these criteria. In this model, a cassette expressing ER(T2)CreER(T2) ( ECE) is inserted at the ATG of the endogenous Aqp2 locus to disrupt Aqp2 function and to express ECE under the control of the Aqp2 promoter. The resulting allele is named Aqp2(ECE). There was no indication of a significant impact of disruption of a copy of Aqp2 on renal function and blood pressure control in adult Aqp2(ECE/+) heterozygotes. Without tamoxifen, Aqp2(ECE) did not activate a Cre-dependent red fluorescence protein (RFP) reporter in adult kidneys. A single injection of tamoxifen (2 mg) to adult mice enabled Aqp2(ECE) to induce robust RFP expression in the whole kidney 24 h postinjection, with the highest recombination efficiency of 95% in the inner medulla. All RFP-labeled cells expressed principal cell markers (Aqp2 and Aqp3), but not intercalated cell markers (V-ATPase B1B2, and carbonic anhydrase II). Hence, Aqp2(ECE) confers principal cell-specific tamoxifen-inducible recombination with absolutely no leakiness, high inducibility, and complete fidelity in cell specificity, which should be an important tool for temporospatial control of target genes in the principal cells and for Aqp2(+) lineage tracing in adult mice. |
