Phenotypes Associated with This Genotype

Genotype
MGI:6226089

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

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

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