Tg(GFAP-CHRM3*)6Kdmc

This transgene expresses a modified human CHRM3 sequence (DREADD or hM3dq) under the control of a human GFAP promoter. The hM3Dq ("DREADD") sequence is a Gq-coupled human M3 muscarinic DREADD (designer receptor exclusively activated by designer drug). To create the hM3Dq sequence, the wildtype human muscarinic 3 receptor (CHRM3) sequence was modified via site-directed mutagenesis to harbor two amino acid substitutions (Y149C<3.33>/A239G<5.46>) 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:215844)