Phenotypes associated with this allele

• Allele Symbol: Chat⁺
• Allele Name: wild type
• Allele ID: MGI:2430122
• Summary: 16 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
ht1	Chat/Slc18a3^tm1.1Vpra/Chat^+	involves: 129S4/SvJae * C57BL/6J	MGI:4367612
ht2	Chat^tm1(cre)Lowl/Chat^+	involves: 129S6/SvEvTac * C57BL/6	MGI:3689725
cn3	Chat^tm2(cre)Lowl/Chat^+ Mapt^tm2(FUS)Neas/Mapt^+	B6.129-Mapt^tm2(FUS)Neas Chat^tm2(cre)Lowl	MGI:5823845
cn4	Chat^tm2(cre)Lowl/Chat^+ Mapt^tm3(FUS)Neas/Mapt^+	B6.129-Mapt^tm3(FUS)Neas Chat^tm2(cre)Lowl	MGI:5823858
cn5	Chat^tm2(cre)Lowl/Chat^+ Mapt^tm3(Sema3e)Arbr/Mapt^tm3(Sema3e)Arbr	involves: 129P2/OlaHsd * 129S6/SvEvTac * C57BL/6	MGI:3848833
cn6	Chat^tm2(cre)Lowl/Chat^+ Mecp2^tm2Bird/Y	involves: 129P2/OlaHsd * 129S6/SvEvTac * C57BL/6J	MGI:6098759
cn7	Chat^tm2(cre)Lowl/Chat^+ Gt(ROSA)26Sor^tm9(CAG-tdTomato)Hze/Gt(ROSA)26Sor^+ Sema6a^Gt(KST069)Byg/Sema6a^Gt(KST069)Byg	involves: 129P2/OlaHsd * 129S6/SvEvTac * C57BL/6NCr	MGI:5562538
cn8	Brsk2^tm2.1Jrs/Brsk2^tm2.1Jrs Chat^tm1(cre)Lowl/Chat^+	involves: 129S1/Sv * 129S6/SvEvTac * 129X1/SvJ	MGI:5524149
cn9	Mc4r^tm1Lowl/Mc4r^tm1Lowl Chat^tm1(cre)Lowl/Chat^+	involves: 129S4/SvJae * 129S6/SvEvTac	MGI:5484740
cn10	Mecp2^tm1Jae/Y Chat^tm2(cre)Lowl/Chat^+	involves: 129S4/SvJae * 129S6/SvEvTac * C57BL/6 * C57BL/6J	MGI:6098756
cn11	Aplp2^tm1Dbo/Aplp2^tm1Dbo App^tm1.1Zhe/App^tm1.1Zhe Chat^tm2(cre)Lowl/Chat^+	involves: 129S6/SvEvTac * 129S7/SvEvBrd * C57BL/6J	MGI:4359069
cn12	Fus^tm1a(EUCOMM)Wtsi/Fus^tm1c(EUCOMM)Wtsi Chat^tm2(cre)Lowl/Chat^+	involves: 129S6/SvEvTac * C3H * C57BL/6 * C57BL/6N	MGI:5823868
cn13	Chat^tm2(cre)Lowl/Chat^+ Stmn2^em2Jmi/Stmn2^em2Jmi	involves: 129S6/SvEvTac * C57BL/6J * C57BL/6N	MGI:7523313
cn14	Chat^tm2(cre)Lowl/Chat^+ Plxna2^tm1a(EUCOMM)Wtsi/Plxna2^tm1Hfu	involves: 129S6/SvEvTac * C57BL/6N * CBA/JNCrlj	MGI:5562536
cn15	Mc4r^tm2Lowl/Mc4r^tm2Lowl Chat^tm1(cre)Lowl/Chat^+ Gt(ROSA)26Sor^tm14(CAG-tdTomato)Hze/Gt(ROSA)26Sor^+	involves: 129S6/SvEvTac * C57BL/6NCr	MGI:5484737
cn16	Chat^tm2(cre)Lowl/Chat^+ Cpeb2^tm1.1Yshu/Cpeb2^tm1.1Yshu	involves: C57BL/6 * C57BL/6J * C57BL/6NJ * SJL/J	MGI:5882505

Genotype
MGI:4367612

ht1

• Allelic Composition: Chat/Slc18a3^tm1.1Vpra/Chat⁺
• Genetic Background: involves: 129S4/SvJae * C57BL/6J

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

homeostasis/metabolism

increased acetylcholine level ( J:153908 )

• increased intracellular acetylcholine level in the brains of adult mice

nervous system

abnormal miniature endplate potential ( J:171696 )

• miniature endplate potential amplitude and frequency are increased compared to in wild-type mice

behavior/neurological

behavior/neurological phenotype ( J:171696 )

N • mice exhibit normal grip force, wire-hanging, gait, and locomotion

Genotype
MGI:3689725

ht2

• Allelic Composition: Chat^tm1(cre)Lowl/Chat⁺
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6

normal phenotype

no abnormal phenotype detected ( J:114556 )

• heterozygotes are viable and fertile; cre recombinase activity is detected in all cholinergic neurons

Genotype
MGI:5823845

cn3

• Allelic Composition: Chat^tm2(cre)Lowl/Chat⁺; Mapt^tm2(FUS)Neas/Mapt⁺
• Genetic Background: B6.129-Mapt^tm2(FUS)Neas Chat^tm2(cre)Lowl

nervous system

motor neuron degeneration ( J:232167 )

• motor neuron loss is seen at P60 but not P30, when 10% of lumbar level 5 (L5) motor neurons are lost and by P360, there are 18.6% fewer motor neurons overall in the L5 segment

abnormal neuromuscular synapse morphology ( J:232167 )

• about 10% denervation of the tibialis anterior neuromuscular junctions (NMJs), first seen at P60 which progresses with age such that at P360, about 25% of NMJs are denervated

• denervation is first noted at P120 in the gastrocnemius muscle where about 10% of NMJs are denervated

• however, even at P360, no denervation is seen in the soleus muscle NMJs

Genotype
MGI:5823858

cn4

• Allelic Composition: Chat^tm2(cre)Lowl/Chat⁺; Mapt^tm3(FUS)Neas/Mapt⁺
• Genetic Background: B6.129-Mapt^tm3(FUS)Neas Chat^tm2(cre)Lowl

nervous system

motor neuron degeneration ( J:232167 )

• significant motor neuron loss is seen at P30 but not P10, and by P360, there are 22.6% fewer motor neurons overall in the lumbar level 5 (L5) segment

abnormal neuromuscular synapse morphology ( J:232167 )

• about 10% denervation of the tibialis anterior neuromuscular junctions, first seen at P20 which progresses with age such that at P360, about 30% of NMJs are denervated

• denervation is first noted at P120 in the gastrocnemius muscle where about 13% of NMJs are denervated

• however, even at P360, no denervation is seen in the soleus muscle NMJs

Genotype
MGI:3848833

cn5

• Allelic Composition: Chat^tm2(cre)Lowl/Chat⁺; Mapt^{tm3(Sema3e)Arbr}/Mapt^{tm3(Sema3e)Arbr}
• Genetic Background: involves: 129P2/OlaHsd * 129S6/SvEvTac * C57BL/6

nervous system

abnormal motor neuron innervation pattern ( J:149553 )

• 23% of triceps motor neurons receive monosynaptic input from triceps afferents compared to 95% in wild-type mice

• however, triceps and cutaneous maximus motor neurons normally lack monosynaptic input from cutaneous maximus afferents

behavior/neurological

behavior/neurological phenotype ( J:149553 )

N • mice exhibit no behavior deficits

Genotype
MGI:6098759

cn6

• Allelic Composition: Chat^tm2(cre)Lowl/Chat⁺; Mecp2^tm2Bird/Y
• Genetic Background: involves: 129P2/OlaHsd * 129S6/SvEvTac * C57BL/6J

respiratory system

abnormal respiration ( J:241788 )

♂ • abnormal hypoxic breathing response

apnea ( J:241788 )

♂

behavior/neurological

behavior/neurological phenotype ( J:241788 )

♂N • mice exhibit normal activity

cardiovascular system

cardiovascular system phenotype ( J:241788 )

♂N • mice exhibit a regular heart rate and show rescue of spontaneous and induced cardiac arrhythmias, long QT, and improved survival

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:241788 )

♂N • mice exhibit a regular body temperature

Genotype
MGI:5562538

cn7

• Allelic Composition: Chat^tm2(cre)Lowl/Chat⁺; Gt(ROSA)26Sor^{tm9(CAG-tdTomato)Hze}/Gt(ROSA)26Sor⁺; Sema6a^{Gt(KST069)Byg}/Sema6a^{Gt(KST069)Byg}
• Genetic Background: involves: 129P2/OlaHsd * 129S6/SvEvTac * C57BL/6NCr

nervous system

abnormal inhibitory postsynaptic currents ( J:202884 )

• starburst amacrine cells in flat mount retinas show excess and aberrant light-evoked inhibitory postsynaptic currents

Genotype
MGI:5524149

cn8

• Allelic Composition: Brsk2^tm2.1Jrs/Brsk2^tm2.1Jrs; Chat^tm1(cre)Lowl/Chat⁺
• Genetic Background: involves: 129S1/Sv * 129S6/SvEvTac * 129X1/SvJ

nervous system

nervous system phenotype ( J:201695 )

N • type Ia proprioceptive sensory neuron projections grow normally to the ventral horn

Genotype
MGI:5484740

cn9

• Allelic Composition: Mc4r^tm1Lowl/Mc4r^tm1Lowl; Chat^tm1(cre)Lowl/Chat⁺
• Genetic Background: involves: 129S4/SvJae * 129S6/SvEvTac

cardiovascular system

hypertension ( J:193452 )

• develop obesity induced hypertension but only during active period

homeostasis/metabolism

increased circulating insulin level ( J:193452 )

• higher plasma insulin levels

Genotype
MGI:6098756

cn10

• Allelic Composition: Mecp2^tm1Jae/Y; Chat^tm2(cre)Lowl/Chat⁺
• Genetic Background: involves: 129S4/SvJae * 129S6/SvEvTac * C57BL/6 * C57BL/6J

mortality/aging

premature death ( J:241788 )

♂ • 67% of mice die early with a median life span of 16 months

cardiovascular system

abnormal heartbeat ( J:241788 )

♂ • irregular heart rhythm and sudden drops in heart rate

increased heart rate variability ( J:241788 )

♂ • increase in heart rate variability during both the light and dark cycles

decreased heart rate ( J:241788 )

♂ • heart rate during the dark cycle is decreased but is not different during the light cycle

ventricular tachycardia ( J:241788 )

♂ • mice show an increased rate of spontaneous ventricular arrhythmias including premature ventricular contractions and nonsustained ventricular tachycardia

ventricular premature beat ( J:241788 )

♂ • mice show an increased rate of spontaneous ventricular arrhythmias including premature ventricular contractions and nonsustained ventricular tachycardia

prolonged QT interval ( J:241788 )

♂

increased response of heart to induced stress ( J:241788 )

♂ • mice are highly susceptible to inducible arrhythmias

homeostasis/metabolism

increased response of heart to induced stress ( J:241788 )

♂ • mice are highly susceptible to inducible arrhythmias

decreased body temperature ( J:241788 )

♂ • mice exhibit decreased temperature during the dark cycle but not the light cycle

behavior/neurological

behavior/neurological phenotype ( J:241788 )

♂N • mice show no differences in activity during the light or dark cycle

respiratory system

respiratory system phenotype ( J:241788 )

♂N • mice do not exhibit increased basal apneas or abnormal hypoxic response

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Rett syndrome		DOID:1206	OMIM:312750 OMIM:613454	J:241788

Genotype
MGI:4359069

cn11

• Allelic Composition: Aplp2^tm1Dbo/Aplp2^tm1Dbo; App^tm1.1Zhe/App^tm1.1Zhe; Chat^tm2(cre)Lowl/Chat⁺
• Genetic Background: involves: 129S6/SvEvTac * 129S7/SvEvBrd * C57BL/6J

nervous system

abnormal neuromuscular synapse morphology ( J:152457 )

• at P0, presynaptic and postsynaptic terminal distribution is diffuse and nerve terminal sprouting occurs unlike in wild-type mice that is not as severe as in Aplp2^tm1Dbo App^tm1.2Zhe double homozygotes

Genotype
MGI:5823868

cn12

• Allelic Composition: Fus^{tm1a(EUCOMM)Wtsi}/Fus^{tm1c(EUCOMM)Wtsi}; Chat^tm2(cre)Lowl/Chat⁺
• Genetic Background: involves: 129S6/SvEvTac * C3H * C57BL/6 * C57BL/6N
• Cell Lines: EPD0667_5_C04

nervous system

nervous system phenotype ( J:232167 )

N • no motor neuron degeneration is seen up to 1 year of age

Genotype
MGI:7523313

cn13

• Allelic Composition: Chat^tm2(cre)Lowl/Chat⁺; Stmn2^em2Jmi/Stmn2^em2Jmi
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6J * C57BL/6N

mortality/aging

preweaning lethality, incomplete penetrance ( J:337175 )

• 16.8% of mice are obtained at P21, indicating a significant deviation from Mendelian ratios

behavior/neurological

decreased grip strength ( J:337175 )

• at 3 months of age, mice show a significant decrease in the latency time (s) to fall from an inverted screen relative to control mice

nervous system

abnormal neuron morphology ( J:337175 )

• mice develop a distal motor neuropathy

abnormal neuromuscular synapse morphology ( J:337175 )

• at 3 months of age, lumbrical muscles show a NMJ phenotype similar to that of single constitutive Stmn2^em1Jmi homozygotes, where most lumbrical muscle fibers are partially denervated with highly fragmented postsynaptic endplates

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
motor peripheral neuropathy		DOID:2477		J:337175

Genotype
MGI:5562536

cn14

• Allelic Composition: Chat^tm2(cre)Lowl/Chat⁺; Plxna2^{tm1a(EUCOMM)Wtsi}/Plxna2^tm1Hfu
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6N * CBA/JNCrlj

vision/eye

abnormal amacrine cell morphology ( J:202884 )

• the starburst amacrine cell (SAC) processes that normally stratify in 2 discrete inner plexiform laminae (S2 and S4) fail to completely segregate from each other

• disruption of the dendritic plexus organization of On but not Off SACs

abnormal retina inner plexiform layer morphology ( J:202884 )

• the starburst amacrine cell (SAC) processes that normally stratify in 2 discrete inner plexiform laminae (S2 and S4) fail to completely segregate from each other

nervous system

abnormal dendrite morphology ( J:202884 )

• the starburst amacrine cell (SAC) processes that normally stratify in 2 discrete inner plexiform laminae (S2 and S4) fail to completely segregate from each other

• disruption of the dendritic plexus organization of On but not Off SACs

abnormal amacrine cell morphology ( J:202884 )

• the starburst amacrine cell (SAC) processes that normally stratify in 2 discrete inner plexiform laminae (S2 and S4) fail to completely segregate from each other

• disruption of the dendritic plexus organization of On but not Off SACs

Genotype
MGI:5484737

cn15

• Allelic Composition: Mc4r^tm2Lowl/Mc4r^tm2Lowl; Chat^tm1(cre)Lowl/Chat⁺; Gt(ROSA)26Sor^{tm14(CAG-tdTomato)Hze}/Gt(ROSA)26Sor⁺
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6NCr

nervous system

nervous system phenotype ( J:193452 )

N • biophysical properties of cholinergic neurons are normal

abnormal nervous system electrophysiology ( J:193452 )

• melanotan II fails to hyperpolarize membrane potentials of all dorsal motor nucleus vagal cholinergic neurons

• similar results with Mc4r agonist THIQ

Genotype
MGI:5882505

cn16

• Allelic Composition: Chat^tm2(cre)Lowl/Chat⁺; Cpeb2^tm1.1Yshu/Cpeb2^tm1.1Yshu
• Genetic Background: involves: C57BL/6 * C57BL/6J * C57BL/6NJ * SJL/J

respiratory system

abnormal whole-body plethysmography ( J:237513 )

• whole-body plethysmography revealed respiratory defects similar to those observed in Cpeb2^tm1.2Yshu homozygotes but with wide individual variation in severity

• however, tidal volume is normal at P1

abnormal breathing pattern ( J:237513 )

• aberrant respiration patterns at P1

decreased pulmonary respiratory rate ( J:237513 )

• reduced respiratory frequency at P1

apnea ( J:237513 )

• increased apneic episodes at P1

• inhalation of nebulized tiotropium, an anticholinergic bronchodilator, reduces apnea frequency to wild-type levels

increased airway responsiveness ( J:237513 )

• significantly increased methacholine-induced airway reactivity in adult mice

homeostasis/metabolism

increased acetylcholine level ( J:237513 )

• increased pulmonary acetylcholine level at P1

increased brain choline acetyltransferase activity ( J:237513 )

• increased choline acetyltransferase (ChAT) expression in the dorsal motor nucleus of vagus (DMNV)