Sirt1^tm3.1Mcby

A knock-in targeting vector was designed to fuse the region encoding the hormone-binding domain (amino acids 281-599 ) of the mouse estrogen receptor alpha to exon 9 of the C-terminal end of the SIRT1 coding region, removing all but the 3' 130 bases of the 1.8 kb 3' Sirt1 UTR. Esr1 contains a point mutation (G525R) that confers selective binding to 4-hydroxy-tamoxifen (4OHT). A loxP-flanked PGK puromycin cassette is located downstream of exon 9. Cre-mediated recombination removed the floxed puro cassette. Sirtuin activity in untreated mouse embryo fibroblasts is 30% of wild-type, increasing 130% in tamoxifen treated cells. (J:241633)