Phenotypes Associated with This Genotype

Genotype
MGI:3700786

• Allelic Composition: Cacna1a^tg/Cacna1a^tg
• Genetic Background: B6.D2-Cacna1a^tg/J

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

behavior/neurological

dystonia ( J:233263 )

• mice exhibit generalized dystonia

ataxia ( J:109231 )

• mice show ataxic behavior around 3-4 weeks of age

abnormal gait ( J:6154 )

• wobbly gait that is first apparent at 3-4 weeks of age and is most prominent in the hindquarters

seizures ( J:6154 )

• spontaneous motor seizures that occur one or more times per day in mice up to 3 months old but seem to decline in frequency during the life span an entire seizure

• an entire seizure lasts about 20-30 minutes and ends abruptly

increased susceptibility to pharmacologically induced seizures ( J:6154 )

• injection with subconvulsant doses of pentylenetetrazole evokes partial motor seizures and spike-wave discharges associated with myoclonic jerks in mutants but not wild-type mice

muscle

dystonia ( J:233263 )

• mice exhibit generalized dystonia

abnormal muscle electrophysiology ( J:233263 )

• abnormal hindlimb movements of mice with generalized dystonia are associated with increases in the amplitude of the electromyograph in both tibialis and gastrocnemius muscles

nervous system

seizures ( J:6154 )

• spontaneous motor seizures that occur one or more times per day in mice up to 3 months old but seem to decline in frequency during the life span an entire seizure

• an entire seizure lasts about 20-30 minutes and ends abruptly

increased susceptibility to pharmacologically induced seizures ( J:6154 )

• injection with subconvulsant doses of pentylenetetrazole evokes partial motor seizures and spike-wave discharges associated with myoclonic jerks in mutants but not wild-type mice

abnormal nervous system electrophysiology ( J:6154 )

• resting ECG shows abnormal bursts of bilaterally synchronous and symmetrical spike waves, 6-7 per second, over the cerebral hemispheres; abnormal bursts last from 0.3 to 10 seconds, occur hundreds of times per day, and can represent up to 10 % of resting ECG activity in an undisturbed adult

• ECG shows that subharmonic spike burst, with 3 spikes per second, is sometimes present

• ECG during seizures most commonly shows low-voltage, desynchronized activity interspersed with long runs of generalized theta waves

decreased excitatory postsynaptic current amplitude ( J:109231 )

• parallel fiber (PF) stimulation is less effective in eliciting EPSCs in ataxic mutants than in wild-type at stimulation intensities of 3-15 Volts

• EPSCs in mice aged 14-20 days (non-ataxic) show a 30% reduction in amplitude; mice aged 28-35 days (ataxic) show a 70% reduction in EPSC amplitude

• when the P/Q-type calcium channel blocker agatoxin is applied to brain slices, PF-EPSCs are reduced in amplitude by 60% compared to wild-type

abnormal paired-pulse inhibition ( J:109231 )

• PPI is observed at 50 msecond interpulse interval, but is reduced compared to wild-type or Cacna1^tg-rol homozygotes in young, non-ataxic mutants; PPI is further reduced in adult ataxic mice compared to young mutants

growth/size/body

decreased body weight ( J:6154 )

• adults weigh on average 7g less than wild-type mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
childhood electroclinical syndrome		DOID:0050704		J:6154
generalized dystonia		DOID:0050835		J:233263