Phenotypes associated with this allele

• Allele Symbol: Cacna1g^tm1Hssh
• Allele Name: targeted mutation 1, Hee-Sup Shin
• Allele ID: MGI:2182962
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Cacna1g^tm1Hssh/Cacna1g^tm1Hssh	involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * C57BL/6J	MGI:5286583
hm2	Cacna1g^tm1Hssh/Cacna1g^tm1Hssh	involves: 129S4/SvJae	MGI:3838397
hm3	Cacna1g^tm1Hssh/Cacna1g^tm1Hssh	involves: 129S4/SvJae * C57BL/6J	MGI:2658915
cx4	Cacna1g^tm1Hssh/Cacna1g^tm1Hssh Gabra1^tm1.1Geh/Gabra1^tm1.1Geh	involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * C57BL/6J	MGI:5286582

Genotype
MGI:5286583

hm1

• Allelic Composition: Cacna1g^tm1Hssh/Cacna1g^tm1Hssh
• Genetic Background: involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * C57BL/6J

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

behavior/neurological

tremors ( J:174980 )

• when moving or suspended by tail but not when relaxed

impaired coordination ( J:174980 )

• on a rotarod, mice exhibit reduced performance compared with wild-type mice

Genotype
MGI:3838397

hm2

• Allelic Composition: Cacna1g^tm1Hssh/Cacna1g^tm1Hssh
• Genetic Background: involves: 129S4/SvJae

cardiovascular system

abnormal cardiovascular system physiology ( J:122634 )

• T-type calcium current in isolated cells from the sinoatrial node and the atrioventricular node and in right atrium myocytes is abolished in mutants

decreased heart rate ( J:122634 )

• sedated mutants exhibit a slower intrinsic in vivo heart rate and conscious unrestrained mutants show bradycardia

• injection of atropine and propranolol to block the autonomic nervous system results in a significantly longer RR interval and a 10% reduction in intrinsic heart rate

abnormal atrioventricular node conduction ( J:122634 )

• delay in atrioventricular conduction; atrial-His conduction times are longer than in wild-type, however His-ventricle intervals are normal

• atrioventricular effective refractory period is significantly longer than in wild-type

• decremental atrial pacing shows that Wenckebach cycle length is significantly longer in mutants

prolonged PQ interval ( J:122634 )

• 9% prolongation of atrioventricular conduction under baseline conditions

• injection of atropine and propranolol to block the autonomic nervous system results in a prolonged PQ interval

abnormal sinoatrial node conduction ( J:122634 )

• prolonged sinoatrial node recovery time

• sinoatrial node cells show a 37% lowing of the cellular beating rate that is accompanied by a 44% reduction of the diastolic depolarization slope

Genotype
MGI:2658915

hm3

• Allelic Composition: Cacna1g^tm1Hssh/Cacna1g^tm1Hssh
• Genetic Background: involves: 129S4/SvJae * C57BL/6J

nervous system

abnormal nervous system physiology ( J:70557 )

• whole-cell voltage clamp analysis of low-voltage activated T-type calcium currents indicates that calcium currents are completely absent in the thalamocortical relay neurons

decreased susceptibility to pharmacologically induced seizures ( J:70557 )

• mutants show resistance to baclofen- or gamma-butyrolactone-induced absence seizures

abnormal spike wave discharge ( J:70557 )

• thalamus is resistant to the generation of spike-and-wave discharges in response to GABA-B receptor activation by baclofen and gamma-butyrolactone injection

• synchronized intra-thalamic oscillations in response to baclofen-mediated hyperpolarization are not observed in mutants

abnormal action potential ( J:70557 )

• thalamocortical relay neurons of the mutant mice lack the burst mode firing of action potentials, however they show a normal pattern of tonic mode firing

behavior/neurological

decreased susceptibility to pharmacologically induced seizures ( J:70557 )

• mutants show resistance to baclofen- or gamma-butyrolactone-induced absence seizures

abnormal spike wave discharge ( J:70557 )

• thalamus is resistant to the generation of spike-and-wave discharges in response to GABA-B receptor activation by baclofen and gamma-butyrolactone injection

• synchronized intra-thalamic oscillations in response to baclofen-mediated hyperpolarization are not observed in mutants

Genotype
MGI:5286582

cx4

• Allelic Composition: Cacna1g^tm1Hssh/Cacna1g^tm1Hssh; Gabra1^tm1.1Geh/Gabra1^tm1.1Geh
• Genetic Background: involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * C57BL/6J

behavior/neurological

abnormal motor learning ( J:174980 )

• on a rotarod, mice fail to exhibit motor learning over several days unlike wild-type mice

tremors ( J:174980 )

• when moving or suspended by tail but not when relaxed

• mice exhibit stronger tremors than Cacna1g^tm1Hssh homozygotes

impaired coordination ( J:174980 )

• on a rotarod, mice exhibit reduced performance compared with wild-type mice and fail to exhibit motor learning over several days

nervous system

decreased Purkinje cell number ( J:174980 )

• mild at 8 months of age

homeostasis/metabolism

decreased physiological sensitivity to xenobiotic ( J:174980 )

• propranolol-treated mice exhibit impaired suppression of tremors compared with similarly treated wild-type mice

• however, mice exhibit normal anti-tremor response to ethanol treatment

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
essential tremor		DOID:4990	OMIM:PS190300	J:174980