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Allele Symbol Allele Name Allele ID |
Chrm3tm1Jwe targeted mutation 1, Jurgen Wess MGI:2155562 |
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| Summary |
7 genotypes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• about 25% reduction in body weight in 14-24 week old males
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• 60% reduction in gonadal fat pad weight in 14-24 week old males
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mean body weights of M3-receptor knockout mice were significantly lower than mean body weights of control mice: 30.7 +/- 1.5 and 35.7 +/- 1.6 g, respectively
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| N |
• basal rates of spontaneously beating mouse atria from homozygous mutant mice are similar to atrial rates in control mice: 472.9 +/- 14.1 and 451.8 +/- 12.0 beats/min, respectively, suggesting that M3 receptors do not modulate basal sinoatrial nodal function
• the potency and maximal decrease in atrial rate to carbamylcholine are comparable in atria from homozygous mutant and control mice, suggesting that M3 receptors do not play a role in the atrial negative chronotropic response to carbamylcholine
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• in the stomach fundus and trachea of homozygous mutant mice, a marked reduction (50-60%) in the maximal response to carbamylcholine is seen compared with control mice
• maximal carbamylcholine-induced contraction of urinary bladder is markedly diminished in homozygous mutant mice, with less than 10% of the contraction in tissue compared to control mice
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• in the stomach fundus of homozygous mutant mice, a marked reduction (50-60%) in the maximal response to carbamylcholine is seen compared with control mice
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• maximal carbamylcholine-induced contraction of urinary bladder is markedly diminished in homozygous mutant mice, with less than 10% of the contraction in tissue compared to control mice
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• in the trachea of homozygous mutant mice, a marked reduction (50-60%) in the maximal response to carbamylcholine is seen compared with control mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• lean phenotype with weight about 22% less than wild-type at 12 weeks of age
(J:67919)
• mutant mice show a 25% reduced body weight that persists throughout the entire life of the animal
(J:91888)
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• females at the end of postnatal week 2 and males at the end of postnatal week 3 show a pronounced decrease in body weight and reduced weight gain
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• hypophagic, ingesting about 30% fewer calories than controls, however, salivation and gastrointestinal motility were normal
• administration of the melanocortin-4 receptor antagonist, AGRP, did not stimulate food intake as it did in wild-type
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• 50-60% reduction in gonadal fat pad weight in 10- and 20-week old males
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• about 6-fold decrease in leptin levels
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• about 25% reduction in triglyceride levels
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• 12 week old males have a small but significant reduction in rectal temperature
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• addition of Oxo-M, a muscarinic agonist, to isolated islets prepared from mutant mice, does not stimulate glucagon secretion unlike the control islets
• the amount of glucagon released by mutant islets in the presence of Oxo-M does not differ significantly from the amount released by mutant islets in the absence of Oxo-M
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• addition of Oxo-M, a muscarinic agonist, to isolated islets prepared from mutant mice, does not lead to a potentiation of glucose-dependent insulin release that is seen in controls
• total pancreatic insulin content is not significantly different between 6-month-old control and mutant mice
• pancreas weight is not not significantly different between control and mutant mice
• the number and size distribution of pancreatic islets are similar in control and mutant mice
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• mutant mice show a significant reduction in blood glucose levels (by 20-50%) starting at age 3 months and persisting up to 1 year of age
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• mutant mice display significantly reduced plasma glucagon levels (30-35% reduction vs. control mice); similar results are seen when mice are fasted
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• 9-fold decrease in serum insulin levels, however have normal glucose levels, did not become hyperglycemic, and maintain normal glucose tolerance
(J:67919)
• 2- to 6-month-old mutant mice show significant reductions (by approximately two- to sixfold) in serum insulin levels as compared to controls
(J:91888)
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• mutant mice show a significant reduction in blood glucose levels compared with controls after glucose administration, indicating that mutant mice clear glucose more efficiently from the circulation than controls
• the glucose-induced spike in serum insulin levels observed 15 min after glucose administration is significantly blunted in mutant mice
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• when injected with insulin, show a more pronounced and prolonged hypoglycemia, indicating increased insulin sensitivity
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• addition of Oxo-M, a muscarinic agonist, to isolated islets prepared from mutant mice, does not stimulate glucagon secretion unlike the control islets
• the amount of glucagon released by mutant islets in the presence of Oxo-M does not differ significantly from the amount released by mutant islets in the absence of Oxo-M
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• addition of Oxo-M, a muscarinic agonist, to isolated islets prepared from mutant mice, does not lead to a potentiation of glucose-dependent insulin release that is seen in controls
• total pancreatic insulin content is not significantly different between 6-month-old control and mutant mice
• pancreas weight is not not significantly different between control and mutant mice
• the number and size distribution of pancreatic islets are similar in control and mutant mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice exhibit normal nociception and anxiety related responses
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• mice exhibit a trend towards impaired cued conditioning compared with wild-type mice
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• mice differ significantly from controls by exhibiting a lower daily quantity of paradoxical sleep, while slow wave sleep amounts remains similar; wake state quantity is slightly increased (but not significantly)
• this is due only to a significant reduction of the number of paradoxical sleep episode, since the mean duration of bouts remained unchanged
• paradoxical sleep quantity decreases more strongly during the 12 h of the dark phase
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• in response to acetylcholine (10 mol/L), adult male homozygotes show an ~80% reduction in dilation of pre-constricted coronary arteries and a ~60% reduction in aortic ring relaxation relative to wild-type males; the residual response to acetylcholine is atropine insensitive
• however, neither significant changes in nitroprusside- or papavarine-induced dilation of coronary arteries nor in papavarine- or A23187-induced relaxation of aortic rings are observed
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• in response to acetylcholine (10 mol/L), adult male homozygotes show an ~80% reduction in dilation of pre-constricted coronary arteries and a ~60% reduction in aortic ring relaxation relative to wild-type males; the residual response to acetylcholine is atropine insensitive
• however, neither significant changes in nitroprusside- or papavarine-induced dilation of coronary arteries nor in papavarine- or A23187-induced relaxation of aortic rings are observed
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• carbamylcholine-induced contractility is inhibited in gallbladder from homozygous mutant mice
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• carbamylcholine-induced contractility is inhibited in gallbladder from homozygous mutant mice
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• application of a low concentration of muscarine (10-8M) induces a bronchoconstriction response similar to control mice, but higher muscarine concentrations (10-6M and 10-4M) results in significantly reduced bronchoconstriction responses in mutant mice
• single administration of 10-4M muscarine to smaller airways from mutant mice results in a significantly reduced rapid bronchoconstriction response
• the transient relaxation response observed with preparations from mutant mice (10% relaxation after initial constriction) is not different from that seen with control mice
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| N |
• facilitation of cortical synaptic transmission induced by 200 micromolar acetylcholine, measured the changes in amplitude of extracellular field potentials (FPs) evoked by stimulation of white matter (WM) and recording in
cortical layer II/III, is similar to controls
• depression of cortical synaptic transmission induced by 1.5mm acetylcholine is not affected
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• fast Fourier transform (FFT) analysis shows that the paradoxical sleep-theta peak
frequency (TPF) values in mutant mice are spectrally distinct during the
dark phase, with a frequency increase in mutants
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• application of a low concentration of muscarine (10-8M) induces a bronchoconstriction response similar to control mice, but higher muscarine concentrations (10-6M and 10-4M) results in significantly reduced bronchoconstriction responses in mutant mice
• single administration of 10-4M muscarine to smaller airways from mutant mice results in a significantly reduced rapid bronchoconstriction response
• the transient relaxation response observed with preparations from mutant mice (10% relaxation after initial constriction) is not different from that seen with control mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• addition of Oxo-M, a muscarinic agonist, to isolated islets prepared from heterozygous mutant mice, results in a significantly reduced potentiation of glucose-dependent insulin release (30-50%) compared to controls
• total pancreatic insulin content is not significantly different between 6-month-old control and mutant mice
• pancreas weight is not not significantly different between control and mutant mice
• the number and size distribution of pancreatic islets were similar in control and mutant mice
|
|
• addition of Oxo-M, a muscarinic agonist, to isolated islets prepared from heterozygous mutant mice, results in a significantly reduced potentiation of glucose-dependent insulin release (30-50%) compared to controls
• total pancreatic insulin content is not significantly different between 6-month-old control and mutant mice
• pancreas weight is not not significantly different between control and mutant mice
• the number and size distribution of pancreatic islets were similar in control and mutant mice
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• 2- to 6-month-old mutant mice show significant reductions (by approximately two- to sixfold) in serum insulin levels as compared to controls
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• the bronchoconstriction response to the cumulative application of muscarine (10-8M to 10-4M) is completely abolished in double homozygous mutant mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• facilitation of cortical synaptic transmission induced by 200 micromolar acetylcholine, measured the changes in amplitude of extracellular field potentials (FPs) evoked by stimulation of white matter (WM) and recording in
cortical layer II/III, is similar to controls
• depression of cortical synaptic transmission induced by 1.5mm acetylcholine is not affected
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Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO) |
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last database update 04/30/2024 MGI 6.23 |
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