Phenotypes associated with this allele

• Allele Symbol: Chrm2^tm1Jwe
• Allele Name: targeted mutation 1, Jurgen Wess
• Allele ID: MGI:2155543
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Chrm2^tm1Jwe/Chrm2^tm1Jwe	B6.129S4-Chrm2^tm1Jwe	MGI:4429952
hm2	Chrm2^tm1Jwe/Chrm2^tm1Jwe	involves: 129S4/SvJae * CF-1	MGI:2662619
ht3	Chrm2^tm1Jwe/Chrm2^+	involves: 129S4/SvJae * CF-1	MGI:3665220
cx4	Chrm2^tm1Jwe/Chrm2^tm1Jwe Chrm3^tm1Jwe/Chrm3^tm1Jwe	involves: 129S4/SvJae * 129S6/SvEvTac * CF-1	MGI:4829438
cx5	Chrm2^tm1Jwe/Chrm2^tm1Jwe Chrm4^tm1Jwe/Chrm4^tm1Jwe	involves: 129S4/SvJae * 129S6/SvEvTac * CF-1	MGI:4829449

Genotype
MGI:4429952

hm1

• Allelic Composition: Chrm2^tm1Jwe/Chrm2^tm1Jwe
• Genetic Background: B6.129S4-Chrm2^tm1Jwe

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

behavior/neurological

abnormal sexual interaction ( J:134260 )

♂ • male mice exhibit a loss of female chasing, sniffing, and mounting behaviors compared with wild-type mice

decreased mounting behavior ( J:134260 )

♂

abnormal vocalization ( J:134260 )

• 6 of 8 mice do not emit ultrasonic vocalizations unlike wild-type mice

• mice exhibit decreased peak frequency of ultrasonic vocalization compared with wild-type mice

• however, duration and bandwidths of ultrasonic vocalizations are normal

Genotype
MGI:2662619

hm2

• Allelic Composition: Chrm2^tm1Jwe/Chrm2^tm1Jwe
• Genetic Background: involves: 129S4/SvJae * CF-1

homeostasis/metabolism

decreased physiological sensitivity to xenobiotic ( J:53061 )

• homozygotes exhibit severely impaired hypothermic response to the centrally acting, nonselective muscarinic agonist oxotremorine

• in contrast, oxotremorine-induced hypersalivation responses remain largely unaffected relative to wild-type littermates

decreased bronchoconstrictive response ( J:104034 )

• compared with bronchi from control animals, mutant bronchi showed similar rapid bronchoconstriction responses but a subsequent relaxation in the presence of 10-4M muscarine

• the sustained bronchoconstriction of smaller airways after a single application of 10-4M muscarine was greatly reduced in mutant mice

• the initial rapid bronchoconstriction response did no differ between mutant and control mice

behavior/neurological

impaired behavioral response to xenobiotic ( J:60451 )

• homozygotes exhibit absence of tremorogenic and severely impaired analgesic responses to the centrally acting, nonselective muscarinic agonist oxotremorine

decreased chemically-elicited antinociception ( J:53061 )

• homozygotes display severely reduced oxotremorine-dependent antinociceptive responses on both the tail-flick and hot plate test relative to wild-type mice

• however, homozygotes show no significant differences in their responsiveness to the opioid analgesic morphine

growth/size/body

decreased body weight ( J:53061 )

• homozygotes are viable and healthy with no morphological or locomotor abnormalities; however, adults weigh ~5% (1.5-2.5 g) less than wild-type littermates

cardiovascular system

cardiovascular system phenotype ( J:102321 )

N • adult male homozygotes show no significant differences in acetylcholine- or sodium nitroprusside-induced dose-dependent dilation of pre-constricted coronary arteries relative to wild-type males

N • similarly, male homozygotes show no significant changes in acetylcholine-, calcium ionophore A23187- or papavarine-induced relaxation of aortic rings relative to wild-type males

abnormal heart rate ( J:60451 )

• spontaneously beating atria derived from mutant mice show a normal basal atrial rate relative to wild-type atria

• strikingly, mutant atrial preparations are unresponsive to the bradycardic effects of muscarinic agonist carbamylcholine, even at the highest carbamylcholine concentration (10^-4 M)

• in contrast, adenosine, a noncholinergic agonist, produces a similar concentration-dependent bradycardia in atria from wild-type and mutant mice

muscle

impaired smooth muscle contractility ( J:60451 , J:125455 )

• homozygotes display impaired carbamylcholine-dependent smooth muscle contractile responses in stomach fundus, urinary bladder, and tracheal smooth muscle preparations, with carbamylcholine potency reduced by a factor of ~2 (J:60451)

• in addition, the affinity of the M2 "selective" receptor antagonist AF-DX116 in inhibiting carbamylcholine-induced smooth muscle contraction is significantly reduced (J:60451)

• a modest inhibition of the maximum contractile response to carbamylcholine is seen in homozygous mutant gallbladders compared with wild-type mice (J:125455)

liver/biliary system

abnormal gallbladder physiology ( J:125455 )

• a modest inhibition of the maximum contractile response to carbamylcholine is seen in homozygous mutant gallbladders compared with wild-type mice

respiratory system

decreased bronchoconstrictive response ( J:104034 )

• compared with bronchi from control animals, mutant bronchi showed similar rapid bronchoconstriction responses but a subsequent relaxation in the presence of 10-4M muscarine

• the sustained bronchoconstriction of smaller airways after a single application of 10-4M muscarine was greatly reduced in mutant mice

• the initial rapid bronchoconstriction response did no differ between mutant and control mice

nervous system

abnormal CNS synaptic transmission ( J:112505 )

• 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 absent or significantly reduced

• depression of cortical synaptic transmission induced by 1.5mm acetylcholine is not affected

Genotype
MGI:3665220

ht3

• Allelic Composition: Chrm2^tm1Jwe/Chrm2⁺
• Genetic Background: involves: 129S4/SvJae * CF-1

homeostasis/metabolism

decreased physiological sensitivity to xenobiotic ( J:53061 )

• heterozygotes exhibit reduced hypothermic responses to the centrally acting, nonselective muscarinic agonist oxotremorine

behavior/neurological

impaired behavioral response to xenobiotic ( J:53061 )

• heterozygotes exhibit absence of tremorogenic responses to the centrally acting, nonselective muscarinic agonist oxotremorine

Genotype
MGI:4829438

cx4

• Allelic Composition: Chrm2^tm1Jwe/Chrm2^tm1Jwe; Chrm3^tm1Jwe/Chrm3^tm1Jwe
• Genetic Background: involves: 129S4/SvJae * 129S6/SvEvTac * CF-1

respiratory system

respiratory system phenotype ( J:104034 )

N • the bronchoconstriction response to the cumulative application of muscarine (10-8M to 10-4M) is completely abolished in double homozygous mutant mice

Genotype
MGI:4829449

cx5

• Allelic Composition: Chrm2^tm1Jwe/Chrm2^tm1Jwe; Chrm4^tm1Jwe/Chrm4^tm1Jwe
• Genetic Background: involves: 129S4/SvJae * 129S6/SvEvTac * CF-1

nervous system

abnormal brain wave pattern ( J:103891 )

• fast Fourier transform (FFT) analysis shows that the paradoxical sleep-theta peak frequency (TPF) values in double homozygous mice are spectrally distinct during the dark phase, with a frequency increase in mutants

• the cumulative theta power is significantly decreased during the light phase for paradoxical sleep in mutant vs. control mice

abnormal CNS synaptic transmission ( J:112505 )

• 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 absent or significantly reduced

• depression of cortical synaptic transmission induced by 1.5mm acetylcholine is not affected

behavior/neurological

behavior/neurological phenotype ( J:103891 )

N • no differences regarding the sleep vigilance states, including paradoxical sleep, are seen in double homozygous mice