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Phenotypes Associated with This Genotype
Genotype
MGI:6226089
Allelic
Composition
Cacna1atm1Lory/Cacna1a+
Genetic
Background
involves: C57BL/6 * C57BL/6J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cacna1atm1Lory mutation (0 available); any Cacna1a mutation (42 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
behavior/neurological
• in the beam test, the numbers of splits corresponding to gait abnormalities are higher in mutants, indicating the presence of a basal ataxia
• 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
• 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
• vertical activity is decreased at 12 and 36 weeks of age
• modest hypoactivity is seen at 36 weeks of age, however, horizontal activity is normal at 12 weeks of age
• 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
• 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
• Purkinje cell dendrites show a decrease of spine number
• mice show a slight increase in cell number in the granule cell layer of the cerebellum at 3 and 45 weeks of age
• 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
• the density of innervations of climbing fibers on Purkinje cells is abnormally increased
• marker analysis suggest the presence of synaptic abnormalities in both parallel fibers and climbing fibers excitatory inputs with an abnormal number of synaptic contacts
• 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
• evoked excitatory postsynaptic currents (eEPSCs) at the parallel fiber-Purkinje cell synapses are strongly diminished
• 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
• 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


Contributing Projects:
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB), Gene Ontology (GO)
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last database update
02/23/2021
MGI 6.16
The Jackson Laboratory