Table 1. Novel mAChR-mutant mouse models.
| Mouse strain | Major phenotypes | Refs |
|---|---|---|
| Chrm1-mutant mice selectively lacking M1 receptors in the forebrain or hippocampal CA3 pyramidal neurons (use of floxed M1 receptor mice) | Lack of mGluR-mediated LTD in the hippocampus, accompanied by changes in presynaptic neurotransmitter release | 116 |
| Mice carrying a floxed Chrm2 gene (floxed M2 receptor mice) | N/A | * |
| Chrm3-mutant mice selectively lacking M3 receptors in specific cell types (use of floxed M3 receptor mice) | Pancreatic β-cells: deficits in glucose tolerance, accompanied by impaired insulin release in vivo | 34 |
| Brain (neurons and glial cells): reduced body size; hypoplasia of the anterior pituitary gland; reduced levels of pituitary and serum growth hormone, as well as prolactin | 117 | |
| Brain (neurons and glial cells): low bone mass, probably owing to enhanced central sympathetic outflow | 118 | |
| Hepatocytes: none (no changes in glucose homeostasis and hepatic glucose fluxes) | 119 | |
| Osteoblasts: none (no changes in bone formation and bone mass) | 118 | |
| Smooth muscle cells (airways): restoration of normal lung function in obese mice | 120 | |
| Chrm3-knock-in mice containing 15 Ser→Ala point mutations within the i3 loop of the M3 receptor | Greatly reduced M3 receptor phosphorylation and impaired arrestin recruitment following M3 receptor activation; deficits in fear conditioning, learning and memory | 121 |
| Impaired glucose tolerance, accompanied by reduced M3 receptor-mediated insulin release from pancreatic islets | 40 | |
| Chrm4-mutant mice selectively lacking M4 receptors in D1 dopamine receptor-expressing neurons (use of floxed M4 receptor mice) | Increased dopamine efflux in the nucleus accumbens; modulation of dopamine-dependent behaviours | 24 |
| Strong reduction of the antipsychotic-like effects of xanomeline in two mouse models of psychosis | 25 | |
| Chrm5-knock-in mice containing an 18-amino-acid deletion within the M5 receptor-i3 loop (residues 369–386) | Reduction in evoked dopamine release from striatal slices | 122 |
LTD, long-term depression; mAChR, muscarinic acetylcholine receptor (five distinct subtypes, denoted M1 to M5, which are encoded by the genes Chrm1 to Chrm5 in mice); mGluR, metabotropic glutamate receptor.
*
J.W. & J. Jeon, unpublished observations.