Phenotypes Associated with This Genotype

Genotype
MGI:3700686

• Allelic Composition: Cacng2^stg/Cacng2^stg
• Genetic Background: B6C3Fe a/a-Cacng2^stg

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

growth/size/body

decreased body size ( J:11008 )

• at 14 days, mutants are smaller than wild-type littermates

behavior/neurological

ataxia ( J:11008 )

• homozygotes can be identified at 14 days by mildly ataxic gait

• males are usually more severely affected than females

impaired swimming ( J:11008 )

• mice show severe disturbances in righting reflex during swimming, with wild underwater tumbling motions

head tossing ( J:11008 )

• at 1 month of age, mice display abnormal head movements both at rest and during activity; frequency of movements increase progressively with age

• movement resembles choreiform head tossing; mice elevate heads vertically and maintain an upward gaze for several seconds

• males are usually more severely affected than females

absence seizures ( J:15527 )

• adults exhibit spontaneous spike-wave seizures; seizures do not appear to increase in mean duration or mean incidence with age

nervous system

absence seizures ( J:15527 )

• adults exhibit spontaneous spike-wave seizures; seizures do not appear to increase in mean duration or mean incidence with age

abnormal neuron differentiation ( J:15527 )

• sprouting of mossy fibers in inner molecular layer and granular cell layer of dentate gyrus increases in mutants compared to wild-type

abnormal hippocampal mossy fiber morphology ( J:15527 )

loss of hippocampal neurons ( J:15527 )

• neuronal density of hilar neurons in hippocampus is reduced by 16% in adult mutants compared to wild-type; this difference only becomes apparent after onset of seizure activity (P17<)

abnormal innervation ( J:15527 )

• mutants show dense mossy fiber staining along the full extent of the dentate gyrus inner molecular layer whereas wild-type show no staining; this is consistently observed in mutants compared to wild-type

• a 48% increase in density of staining is seen within the inner molecular layer-granular cell layer of adult mutants

• no mossy fiber sprouting is observed prior to seizure onset (at P15), but progressively increasing staining specific for mossy fibers is observed from P30-6 months of age

abnormal CNS synapse formation ( J:15527 )

• the ectopic terminals that are seen do not appear to form synapses with dendrites of basket or granule cells

abnormal brain wave pattern ( J:11008 , J:15527 )

• electrocorticographic (ECoG) recordings from young adults display prolonged high-amplitue (500uV-1mV), bilaterally symmetrical discharges from neocortex, accompanied by behavioral immobility for the duration of the discharge (J:11008)

• paroxysmal spike bursts show 6-7 spikes/second frequencies, with discharge durations of 1-66 seconds; mean rate or discharge activity is 125/hr (J:11008)

• adults show highly reproducible pattern of spontaneous bilaterally symmetrical 6-7/second spike-wave discharges in cortical and hippocampal regions (J:15527)

• seizure rate ranges from 43-209 discharges/hour with durations ranging from 1-66 seconds with a mean of 4-6 seconds (J:15527)

• patterned spike-wave synchronous discharges represent ~20% of total EEG activity in adult mice (J:15527)

• no spike-wave discharges are recorded in P15 mice but are always present by P18; discharges in immature animals can display slightly slower spike frequency (4-5/sec) but are identical to those seen in adults (J:15527)

reproductive system

male infertility ( J:11008 )

♂ • males are infertile

cellular

abnormal neuron differentiation ( J:15527 )

• sprouting of mossy fibers in inner molecular layer and granular cell layer of dentate gyrus increases in mutants compared to wild-type