Phenotypes associated with this allele

• Allele Symbol: Cacna1a⁺
• Allele Name: wild type
• Allele ID: MGI:2152752
• Summary: 14 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
ht1	Cacna1a^Tg-5J/Cacna1a^+	B10.Cg-Cacna1a^Tg-5J	MGI:3804050
ht2	Cacna1a^tm1Maag/Cacna1a^+	B6.129P2-Cacna1a^tm1Maag	MGI:3836259
ht3	Cacna1a^tm3Maag/Cacna1a^+	B6.129P2-Cacna1a^tm3Maag	MGI:3836257
ht4	Cacna1a^tm2.1Kewa/Cacna1a^+	B6.Cg-Cacna1a^tm2.1Kewa	MGI:5467735
ht5	Cacna1a^em1(IMPC)H/Cacna1a^+	C57BL/6NTac-Cacna1a^em1(IMPC)H/H	MGI:7471904
ht6	Cacna1a^Wb/Cacna1a^+	either: C3.B6-Cacna1a^Wb or (involves: C3H/HeJ * C57BL/6J)	MGI:3706671
ht7	Cacna1a^tm3Maag/Cacna1a^+	involves: 129P2/OlaHsd	MGI:5487278
ht8	Cacna1a^Tg-7J/Cacna1a^+	involves: 129P2/OlaHsd * C57BL/6J	MGI:4459426
ht9	Cacna1a^tm1(CACNA1A)Ttan/Cacna1a^+	involves: 129S4/SvJae	MGI:3718377
ht10	Cacna1a^tm3Hzo/Cacna1a^+	involves: 129S/SvEv * C57BL/6J	MGI:3810402
ht11	Cacna1a^tg-la/Cacna1a^+	involves: AKR/J * C3H/HeJ * C57BL/6J	MGI:3710961
ht12	Cacna1a^tg-rol/Cacna1a^+	involves: C3Hf/Nga * C57BL/6 * SIII	MGI:4834664
ht13	Cacna1a^tm1Lory/Cacna1a^+	involves: C57BL/6 * C57BL/6J	MGI:6226089
cx14	Cacna1a^Tg-5J/Cacna1a^+ Tg(Pvalb-EGFP)B20Zjh/?	involves: BALB/cByJ * C57BL/6 * C57BL/10J	MGI:3803746

Genotype
MGI:3804050

ht1

• Allelic Composition: Cacna1a^Tg-5J/Cacna1a⁺
• Genetic Background: B10.Cg-Cacna1a^Tg-5J

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

behavior/neurological

ataxia ( J:137816 )

• gait is shaky and hindlimbs are splayed laterally from body

nervous system

abnormal Purkinje cell morphology ( J:137816 )

• Purkinje cell arbor is reduced in complexity and in overall dendritic mass

abnormal Purkinje cell dendrite morphology ( J:137816 )

• tips of distal dendrites have an abnormal serpentine-like appearance

• shafts of dendrites exhibit a thickening in the upper molecular layer

abnormal axon morphology ( J:137816 )

• axonal swelling is observed in Purkinje cells

abnormal nervous system electrophysiology ( J:137816 )

• calcium channel voltage activation and inactivation is shifted to lower voltages

Genotype
MGI:3836259

ht2

• Allelic Composition: Cacna1a^tm1Maag/Cacna1a⁺
• Genetic Background: B6.129P2-Cacna1a^tm1Maag

nervous system

abnormal nervous system electrophysiology ( J:144701 )

• following induction with KCl, spreading depression frequency and propagation speed are increased compared to in wild-type mice but not as much as in homozygotes

• KCl-induced cortical spreading depressions propagate into the striatum unlike in wild-type mice but not as much as in homozygous mice

• mice exhibit 1 or more recurrent spreading depressions following brief topical KCl application and extensive washing unlike in wild-type mice

homeostasis/metabolism

abnormal physiological response to xenobiotic ( J:144701 )

• topical application of 300 mM KCl induces a single spreading depression that causes impairments in coordination not observed in wild-type mice that are not as severe as in homozygous mice

• KCl-induced cortical spreading depressions propagate into the striatum unlike in wild-type mice but not as much as in homozygous mice

• mice exhibit 1 or more recurrent spreading depressions following brief topical KCl application and extensive washing unlike in wild-type mice

Genotype
MGI:3836257

ht3

• Allelic Composition: Cacna1a^tm3Maag/Cacna1a⁺
• Genetic Background: B6.129P2-Cacna1a^tm3Maag

nervous system

abnormal nervous system electrophysiology ( J:144701 )

• following induction with KCl, spreading depression frequency and propagation speed are increased compared to in wild-type mice but not as much as in homozygotes

• KCl-induced cortical spreading depressions propagate into the striatum unlike in wild-type mice but not as much as in homozygous mice

• mice exhibit 1 or more recurrent spreading depressions following brief topical KCl application and extensive washing unlike in wild-type mice

• however, recovery of cortical evoked potentials after KCl-induced spreading depression is normal

homeostasis/metabolism

abnormal physiological response to xenobiotic ( J:144701 )

• topical application of 300 mM KCl induces a single spreading depression that causes impairments in coordination not observed in wild-type mice that are not as severe as in homozygous mice

• KCl-induced cortical spreading depressions propagate into the striatum unlike in wild-type mice but not as much as in homozygous mice

• mice exhibit 1 or more recurrent spreading depressions following brief topical KCl application and extensive washing unlike in wild-type mice

• however, recovery of cortical evoked potentials after KCl-induced spreading depression is normal

behavior/neurological

enhanced behavioral response to xenobiotic ( J:144701 )

• topical application of 300 mM KCl induces a single spreading depression that causes impairments in coordination not observed in wild-type mice that are not as severe as in homozygous mice

Genotype
MGI:5467735

ht4

• Allelic Composition: Cacna1a^tm2.1Kewa/Cacna1a⁺
• Genetic Background: B6.Cg-Cacna1a^tm2.1Kewa

behavior/neurological

abnormal motor coordination/balance ( J:190729 )

• impaired performance on the rotarod at 18 months of age

ataxia ( J:190729 )

• develops at about 1 year of age

nervous system

Purkinje cell degeneration ( J:190729 )

• cell loss is detected at 100 weeks of age

• cytoplasmic inclusions are detected in the cerebellum after 15 weeks of age and become more evident with age

Genotype
MGI:7471904

ht5

• Allelic Composition: Cacna1a^em1(IMPC)H/Cacna1a⁺
• Genetic Background: C57BL/6NTac-Cacna1a^em1(IMPC)H/H

Data Sources

IMPC Data for Cacna1a

behavior/neurological

increased freezing behavior ( J:211773 )

♂

IMPC - HAR

Genotype
MGI:3706671

ht6

• Allelic Composition: Cacna1a^Wb/Cacna1a⁺
• Genetic Background: either: C3.B6-Cacna1a^Wb or (involves: C3H/HeJ * C57BL/6J)

mortality/aging

mortality/aging ( J:119639 )

N • the lifespan of mice heterozygous for this mutation is similar to that of wild-type mice

growth/size/body

growth/size/body region phenotype ( J:119639 )

N • the body size of heterozygous mutant mice is normal

behavior/neurological

behavior/neurological phenotype ( J:119639 )

N • neither heterozygous nor homozygous mutant mice exhibit paroxysmal dyskinesia or motor seizure as occurs in mice homozygous for some recessive mutations at this locus

N • the grip strength of heterozygous mutants is similar to that of wild-type mice

ataxia ( J:119639 )

• by postnatal days (P)21-28, mice heterozygous for this mutation can be recognized by their unsteady gait

• by P21-28, heterozygous mutant mice can be identified by their wide stance, with their hind legs splayed and their bodies carried low

• the motor abnormalities of mice heterozygous for this mutation mice do not progress with age

impaired coordination ( J:119639 )

• motor function testing demonstrates significant motor function deficits in heterozygous mutant mice, though less severe than in homozygous mutants

• the hindlimb extension reflex of heterozygous mice is abnormal

• in the inclined-plane test, heterozygous mutant mice take significantly longer than wild-type mice to cross the inclined platform

• in the rotarod test, heterozygous mutants have significantly greater difficulty remaining on the rod than do wild-type mice, even at low speeds

• the motor abnormalities of heterozygous mutant mice do not progress with age

impaired fine motor coordination ( J:119639 )

• in the narrow-beam cross, heterozygous mutants exhibit more difficulty maneuvering than do wild-type mice, indicating deficient fine motor control

decreased locomotor activity ( J:119639 )

• by P21-28, mice heterozygous for this mutation can be seen to exhibit reduced locomotor activity

nervous system

nervous system phenotype ( J:119639 )

N • cerebellar sections show neither Purkinje cell loss nor a decrease in the size of the granule cell layer in heterozygous or homozygous mutant mice

thin cerebellar molecular layer ( J:119639 )

• the molecular layer of the cerebellum in sections from 8 week-old homozygous and heterozygous mutant mice is significantly reduced in thickness and total area relative to that of wild-type control mice

cerebellum atrophy ( J:119639 )

• brain MRI of 8-week-old mutant mice reveals significant cerebellar atrophy, primarily in the superior and medial regions, including lobes III and V; the cerebellum-to-brain volume ratio of heterozygous mutants is 7% lower than that of wild-type controls (P<0.01)

Genotype
MGI:5487278

ht7

• Allelic Composition: Cacna1a^tm3Maag/Cacna1a⁺
• Genetic Background: involves: 129P2/OlaHsd

homeostasis/metabolism

increased susceptibility to ischemic brain injury ( J:193793 )

• mice show increased vulnerability to ischemic stroke, developing an earlier onset of anoxic depolarization after filament occlusion of the middle cerebral artery

increased cerebral infarct size ( J:193793 )

• transient filament occlusion of the middle cerebral artery for 30 minutes produces larger infarcts than in wild-type mice

• females show more striking increases in infarct volume than males

• treatment with the NMDA antagonist MK-801 significantly reduces infarct volume by 45% in mutants compared with only 23% in wild-type mice

mortality/aging

increased susceptibility to induced morbidity/mortality ( J:193793 )

♀ • females exhibit more than 60% mortality between 24 and 96 hours following transient filament occlusion of the cerebral artery for 30 minutes

nervous system

increased susceptibility to ischemic brain injury ( J:193793 )

• mice show increased vulnerability to ischemic stroke, developing an earlier onset of anoxic depolarization after filament occlusion of the middle cerebral artery

increased cerebral infarct size ( J:193793 )

• transient filament occlusion of the middle cerebral artery for 30 minutes produces larger infarcts than in wild-type mice

• females show more striking increases in infarct volume than males

• treatment with the NMDA antagonist MK-801 significantly reduces infarct volume by 45% in mutants compared with only 23% in wild-type mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
familial hemiplegic migraine		DOID:0060178		J:193793

Genotype
MGI:4459426

ht8

• Allelic Composition: Cacna1a^Tg-7J/Cacna1a⁺
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6J

behavior/neurological

ataxia ( J:161271 )

abnormal gait ( J:161271 )

• shaky, wobbly walk with the hindquarters affected the most, apparent after wean age

Genotype
MGI:3718377

ht9

• Allelic Composition: Cacna1a^{tm1(CACNA1A)Ttan}/Cacna1a⁺
• Genetic Background: involves: 129S4/SvJae

behavior/neurological

impaired coordination ( J:123243 )

• at 6 and 12 months of age, mice exhibit a shortened latency to call compared to wild-type mice

• however, at 6 and 9 months of age, mice exhibit longer retention time compared to wild-type mice and other measures of coordination are normal

Genotype
MGI:3810402

ht10

• Allelic Composition: Cacna1a^tm3Hzo/Cacna1a⁺
• Genetic Background: involves: 129S/SvEv * C57BL/6J

behavior/neurological

impaired coordination ( J:139488 )

• at 19 months, mice exhibit impaired performance in a rotarod compared to wild-type mice

Genotype
MGI:3710961

ht11

• Allelic Composition: Cacna1a^tg-la/Cacna1a⁺
• Genetic Background: involves: AKR/J * C3H/HeJ * C57BL/6J

behavior/neurological

behavior/neurological phenotype ( J:119639 )

N • genotyping of phenotypically normal progeny from a cross between mice heterozygous for Cacna1a^Wb and for Cacna1a^tg-la demonstrated that all were either wild-type (Cacna1a⁺/Cacna1a⁺) or heterozygous for Cacna1a^tg-la

Genotype
MGI:4834664

ht12

• Allelic Composition: Cacna1a^tg-rol/Cacna1a⁺
• Genetic Background: involves: C3Hf/Nga * C57BL/6 * SIII

homeostasis/metabolism

abnormal glucose homeostasis ( J:3611 )

• mice show an intermediate increase in local cerebral glucose utilization in the basal ganglia structures such as the globus pallidus, substantia nigra pars reticulata, and subthalamic nucleus

nervous system

abnormal nervous system physiology ( J:3611 )

• mice show an intermediate increase in local cerebral glucose utilization in the basal ganglia structures such as the globus pallidus, substantia nigra pars reticulata, and subthalamic nucleus

Genotype
MGI:6226089

ht13

• Allelic Composition: Cacna1a^tm1Lory/Cacna1a⁺
• Genetic Background: involves: C57BL/6 * C57BL/6J

behavior/neurological

ataxia ( J:258570 )

• in the beam test, the numbers of splits corresponding to gait abnormalities are higher in mutants, indicating the presence of a basal ataxia

impaired coordination ( J:258570 )

• mice spend less time on the rotarod at 3 to 12 weeks of age, with this motor impairment appearing at 3 weeks and remaining stable with age as 36 week old mice have a similar level of impairment

• noradrenergic activation with isoproterenol treatment increases motor dysfunction on the rotarod test with no signs of dyskinesia

• however, mice do not show signs of attacks of dyskinesia during cage handling or behavioral tests

decreased grip strength ( J:258570 )

• mice exhibit a lower ability to hold onto the grid in the inverted grid, indicating muscular deficits

• mice show decreased muscle strength in the front limbs as well as for the 4 limbs in the grip test at 12 and 36 weeks of age

decreased vertical activity ( J:258570 )

• vertical activity is decreased at 12 and 36 weeks of age

decreased locomotor activity ( J:258570 )

• modest hypoactivity is seen at 36 weeks of age, however, horizontal activity is normal at 12 weeks of age

absence seizures ( J:258570 )

• electroencephalograms show the presence of bilateral generalized abnormal spike-wave discharges, indicating spontaneous non-convulsive generalized seizures

• spontaneous seizures have an intrinsic frequency of 6-8 Hz and appear more than 4 times per hour

nervous system

absence seizures ( J:258570 )

• electroencephalograms show the presence of bilateral generalized abnormal spike-wave discharges, indicating spontaneous non-convulsive generalized seizures

• spontaneous seizures have an intrinsic frequency of 6-8 Hz and appear more than 4 times per hour

abnormal Purkinje cell dendrite morphology ( J:258570 )

• Purkinje cell dendrites show a decrease of spine number

increased cerebellar granule cell number ( J:258570 )

• mice show a slight increase in cell number in the granule cell layer of the cerebellum at 3 and 45 weeks of age

abnormal cerebellar molecular layer ( J:258570 )

• mice show a slight increase in cell number in the molecular layer of the cerebellum at 3 and 45 weeks of age

• however, no loss of Purkinje cells is seen

abnormal Purkinje cell innervation ( J:258570 )

• the density of innervations of climbing fibers on Purkinje cells is abnormally increased

abnormal synapse morphology ( J:258570 )

• marker analysis suggest the presence of synaptic abnormalities in both parallel fibers and climbing fibers excitatory inputs with an abnormal number of synaptic contacts

abnormal action potential ( J:258570 )

• spontaneous activity of Purkinje cells is affected, with longer mean interspike interval of spontaneous action potential in Purkinje cells associated with an increase in the coefficient of variation of the interspike

abnormal excitatory postsynaptic currents ( J:258570 )

• evoked excitatory postsynaptic currents (eEPSCs) at the parallel fiber-Purkinje cell synapses are strongly diminished

decreased excitatory postsynaptic current amplitude ( J:258570 )

• following electrical stimulations of parallel fibers with pulses of increasing intensities, the mean amplitudes of evoked excitatory postsynaptic currents (eEPSCs) are decreased at parallel fiber-Purkinje cell synapses at all intensities, indicating decreased synaptic strength of parallel fiber excitatory inputs on Purkinje cells

increased excitatory postsynaptic current amplitude ( J:258570 )

• climbing fiber (CF)-Purkinje cell (PC) synaptic transmission is abnormally elevated due to an increase of synaptic contacts, with mice showing a larger mean eEPSC amplitude at CF-PC synapses

• however, the paired-pulse ratio is not modified, indicating that the increase in synaptic strength is the result of an anomalous number of release sites rather than an increase in the probability of release at each synaptic site

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
episodic ataxia type 2		DOID:0050990	OMIM:108500	J:258570

Genotype
MGI:3803746

cx14

• Allelic Composition: Cacna1a^Tg-5J/Cacna1a⁺; Tg(Pvalb-EGFP)B20Zjh/?
• Genetic Background: involves: BALB/cByJ * C57BL/6 * C57BL/10J

nervous system

abnormal Purkinje cell morphology ( J:137816 )

• GFP-stained Purkinje cells exhibit decreased branching

• primary branches have novel GFP-negative vacuoles that do not impede cytoplasmic flow