Gt(ROSA)26Sor^{tm8(CAG-CHRM3*)Jcbr}

The targeting construct contained the CAG promoter (chicken beta actin promoter with CMV enhancers), a floxed neomycin-Westphal stop sequence (WSS) cassette, and a modified Gq-coupled human M3 muscarinic receptor (CHRM3) gene. The wild-type human muscarinic 3 receptor sequence was modified via site-directed mutagenesis to harbor two amino acid substitutions (Y149C and A239G) that abolish receptor affinity for the native ligand, acetylcholine (ACh), but allow receptor binding and subsequent activation by the small drug-like molecule clozapine-N-oxide (CNO). (J:234407)