AAV with tMCK promoter driven CreERT2

This AAV expresses CreERT2 driven by a muscle tMCK promoter.

tMCK is constructed by ligating a triple tandem copies of mouse MCK enhancer ( about200 bps each) to the ~100bp mouse MCK basal promoter.). This promoter shows extremely sensitive tissue-specificity: (1) In differentiated C2C12 myotubes, the tMCK promoter is 30-50 fold stronger than the Enh358MCK promoter and 10-20 fold stronger than the CMV promoter; (2) In muscle tissue, tMCK promoter is 15-20 fold stronger than the Enh358MCK promoter, and 3-5 fold stronger than the CMV promoter; (3) Strong tissue-specificity: in liver tissue, the expression level from tMCK promoter is only about 0.3-0.5% of that of the CMV promoter.

A mutated form of estrogen ligand-binding domain (ERT2) that binds to synthetic antagonists (such as tamoxifen or its derivative 4-hydroxy-tamoxifen) but not to circulating estrogen, was fused to the Cre recombinase (Cre) to create CreERT2 (also known as "inducible Cre"). When tamoxifen binds to CreERT2, it induces a conformational change of CreERT2, leading to its nuclear translocation, followed by Cre/Lox-mediated recombination.