Phenotypes associated with this allele

• Allele Symbol: Cacna1a^tm1Maag
• Allele Name: targeted mutation 1, Arn van den Maagdenberg
• Allele ID: MGI:3037859
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Cacna1a^tm1Maag/Cacna1a^tm1Maag	B6.129P2-Cacna1a^tm1Maag	MGI:3836258
hm2	Cacna1a^tm1Maag/Cacna1a^tm1Maag	involves: 129P2/OlaHsd * C57BL/6J	MGI:3037958
ht3	Cacna1a^tm1Maag/Cacna1a^+	B6.129P2-Cacna1a^tm1Maag	MGI:3836259

Genotype
MGI:3836258

hm1

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

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

Neurological deficits after spreading depression in Cacna1a^tm1Maag/Cacna1a^tm1Maag and Cacna1a^tm3Maag/Cacna1a^tm3Maag mice

nervous system

increased susceptibility to ischemic brain injury ( J:193793 )

• mice show increased vulnerability to ischemic stroke, developing an earlier onset of anoxic depolarization and more frequent peri-infarct depolarizations after filament occlusion of the middle cerebral artery associated with rapid expansion of infarct core on diffusion-weighted magnetic resonance imaging

increased cerebral infarct size ( J:193793 )

• transient filament occlusion of the middle cerebral artery for 1 hour produces larger infarcts than in wild-type mice, with more severe cortical involvement

abnormal nervous system electrophysiology ( J:144701 )

• following induction with KCl, spreading depression frequency and propagation speed are increased, especially in females, compared to in wild-type mice but not as much as in Cacna1a^tm1Caya homozygotes

• ovariectomy and cessation of estrous cycling eliminates sex differences

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

• KCl-induced cortical spreading depression propagates into the striatum unlike in wild-type mice but with lesser frequency and longer latencies than in Cacna1a^tm1Caya homozygotes

• corticaostriatal propogation of KCl-induced cortical spreading depression is greater in female mice than in male mice

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

behavior/neurological

enhanced behavioral response to xenobiotic ( J:144701 )

• topical application of 300 mM KCl induces a single spreading depression that causes hemiplegia, leaning, circling, and impaired coordination unlike in similarly treated wild-type mice

abnormal posture ( J:144701 )

• a single spreading depression induced by KCl causes hemiplegia with leaning and circling unlike in wild-type mice

hemiplegia ( J:144701 )

• a single spreading depression induced by KCl causes hemiplegia with leaning and circling unlike in wild-type mice

circling ( J:144701 )

• a single spreading depression induced by KCl causes hemiplegia with leaning and circling 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 hemiplegia, leaning, circling, and impaired coordination unlike in similarly treated wild-type mice

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

• KCl-induced cortical spreading depression propagates into the striatum unlike in wild-type mice but with lesser frequency and longer latencies than in Cacna1a^tm1Caya homozygotes

• corticaostriatal propogation of KCl-induced cortical spreading depression is greater in female mice than in male mice

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

increased susceptibility to ischemic brain injury ( J:193793 )

• mice show increased vulnerability to ischemic stroke, developing an earlier onset of anoxic depolarization and more frequent peri-infarct depolarizations after filament occlusion of the middle cerebral artery associated with rapid expansion of infarct core on diffusion-weighted magnetic resonance imaging

increased cerebral infarct size ( J:193793 )

• transient filament occlusion of the middle cerebral artery for 1 hour produces larger infarcts than in wild-type mice, with more severe cortical involvement

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
familial hemiplegic migraine		DOID:0060178		J:144701 , J:193793

Genotype
MGI:3037958

hm2

• Allelic Composition: Cacna1a^tm1Maag/Cacna1a^tm1Maag
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6J

nervous system

abnormal CNS synaptic transmission ( J:88693 )

• a decrease in the threshold for induction and an increase in propagation velocity of cortical spreading depression (a wave of transient intense spike activity followed by long-lasting neuronal suppression that crosses the cortex)

• mutants are viable, fertile, and display no overt phenotype unlike Cacna1a null mutants

abnormal PNS synaptic transmission ( J:88693 )

• increased neurotransmission at the neuromuscular junction under specific conditions

abnormal miniature endplate potential ( J:88693 )

• miniature endplate potential (spontaneous postsynaptic depolarization resulting from uniquantal acetylcholine release) frequency is increased

abnormal channel response ( J:88693 )

• mutant Ca_v2.1 channels activate at lower voltages and open more readily than wild-type channels

• the density of functional Ca_v2.1 channels in mutants is unaffected

• other Ca²⁺ channels are unaffected

abnormal synaptic acetylcholine release ( J:88693 )

• at the neuromuscular junction acetylcholine release when the concentration of Ca²⁺ is below saturation concentrations is significantly increased

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
familial hemiplegic migraine		DOID:0060178		J:88693

Genotype
MGI:3836259

ht3

• 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