Phenotypes associated with this allele

• Allele Symbol: Cacng2^stg
• Allele Name: stargazer
• Allele ID: MGI:1856548
• Summary: 8 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Cacng2^stg/Cacng2^stg	B6C3Fe a/a-Cacng2^stg	MGI:3700686
hm2	Cacng2^stg/Cacng2^stg	B6C3Fe a/a-Cacng2^stg/J	MGI:3580906
hm3	Cacng2^stg/Cacng2^stg	involves: A/J	MGI:3810419
hm4	Cacng2^stg/Cacng2^stg	involves: A/J * C3HeB/FeJ * C57BL/6J	MGI:3700749
hm5	Cacng2^stg/Cacng2^stg	Not Specified	MGI:3812002
cx6	Cacng2^stg/Cacng2^stg Cacng8^tm1.1Suto/Cacng8^tm1.1Suto	involves: A/J	MGI:5307143
cx7	Cacng2^stg/Cacng2^stg Cacng3^tm1Ran/Cacng3^tm1Ran	involves: A/J	MGI:3810418
cx8	Cacng2^stg/Cacng2^stg Cacng4^tm1Frk/Cacng4^tm1Frk	involves: B6C3Fe a/a-Cacng2^stg/J * B6.129-Cacng4^tm1Frk/J	MGI:3531476

Genotype
MGI:3700686

hm1

• 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

Genotype
MGI:3580906

hm2

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

The Cacng2^stg/Cacng2^stg mouse

behavior/neurological

impaired righting response ( J:91987 )

• when mice are dropped supine from height of 50 cm, mutants show poor air-righting performance, whereas control mice land on their feet ~100% of the time and toxin-treated normal controls land feet-first on ~50% of tests

• when placed inside a tube and inverted to supine position, mutants remain inverted for duration (60 s) of test whereas controls right themselves within a few seconds

• after 30 minutes of intermittent horizontal rotation, control mice display a significant decrease in spontaneous movement, but mutants do not show a decrease

decreased startle reflex ( J:91987 )

• mutants lack the acoustic startle reflex (ASR), but startle reflex to somatic sensory stimuli such as air puffs is intact

impaired coordination ( J:91987 )

• mutants can only stay on the grid for 60 seconds, coinciding with the turn to 90 degrees, in a cling test; control mice can hang on to the grid for ~180 seconds, including complete inversion of the grid

• in the rotarod test, mutants and drug-treated control mice fall off the rod immediately, often before it begins to move, whereas normal controls can walk for ~the full 5 minute test period

impaired swimming ( J:91987 )

• mutants cannot keep their heads above water during swimming and rapidly begin a spiraling motion underwater and drown if not rescued

decreased vertical activity ( J:91987 )

hyperactivity ( J:91987 )

• in photocell activity chambers, mutants display 3-4-fold higher activity compared to control mice while vestibular toxin-treated controls have 10-fold increased activity

stereotypic behavior ( J:91987 )

• stereotypic behaviors like circling or abnormal head movements, are evident in all mutants at 2-3 weeks of age, and persist throughout observation period (>1 year)

head bobbing ( J:91987 )

• in open field tests, mutants display rapid vertical bobbing head movements

head shaking ( J:91987 )

• mice show rapid sideways wagging movements of the head during open field tests

head tossing ( J:91987 )

• mice show occasional episodes of exaggerated and sustained, elevation of the head, resembling retrocollis, during open field observations

circling ( J:91987 )

• in open field test, mice exhibit circling to the left or right; controls do not while in vestibular toxin-treated normal controls, circling is exacerbated compared to mutants

hearing/vestibular/ear

abnormal vestibular hair cell morphology ( J:91987 )

• vacuole-like defects measuring 15-25 um are seen in the vestibular epithelium

• cells are disorganized in sensory epithelium; some supporting cell nuclei lose contact with the basement membrane and occupy locations higher in the epithelium

abnormal type I vestibular cell ( J:91987 )

• afferent nerve calyces surrounding type I hair cells lack the fullness and rich mitochondrial content seen in controls; large vacuole-like defects appear to be localized inside afferent calyces

• these vacuoles are surrounded by normal but small and crowded mitochondria and contain scanty debris like cytosol or mitochondria

abnormal crista ampullaris morphology ( J:91987 )

• crista show a reduction density of hair cells compared to controls

increased or absent threshold for auditory brainstem response ( J:91987 )

• ABR thresholds for click as a stimulus are normal, with a trend toward increased thresholds for 8 and 16 kHz tone stimuli in mutants (not reaching significance, though)

nervous system

abnormal vestibular hair cell morphology ( J:91987 )

• vacuole-like defects measuring 15-25 um are seen in the vestibular epithelium

• cells are disorganized in sensory epithelium; some supporting cell nuclei lose contact with the basement membrane and occupy locations higher in the epithelium

abnormal type I vestibular cell ( J:91987 )

• afferent nerve calyces surrounding type I hair cells lack the fullness and rich mitochondrial content seen in controls; large vacuole-like defects appear to be localized inside afferent calyces

• these vacuoles are surrounded by normal but small and crowded mitochondria and contain scanty debris like cytosol or mitochondria

abnormal thalamus morphology ( J:192431 )

• global loss of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepripionic acid (AMPA) receptors in nucleus reticularis and a selective loss at corticothalamic synapses in inhibitory neurons of the nucleus reticularis thalamus

• however, no loss of AMPA receptors is seen at corticothalamic synapses in excitatory relay neurons in the thalamic ventral posterior region

abnormal Purkinje cell innervation ( J:116541 )

• there are more parallel fiber- Purkinje spine synapses with smaller presynsaptic terminal compared to the postsynaptic spine

• there is a 43% reduction in the mean area of the presynaptic terminals in mutants

• synaptic profile in wild-type shows >80% of synapses having larger parallel fiber varicosities than postsynaptic Purkinje cell spines, while in mutants there is ~equal distribution of synapses with larger parallel fiber area than postsynaptic Purkinje cell spine, those with equal pre- and postsynaptic areas, or with smaller parallel fiber varicosity than the postsynaptic Purkinje cell spine

abnormal CNS synapse formation ( J:116541 )

• synaptic size appears smaller

decreased CNS synapse formation ( J:116541 )

• mutants have lower synaptic density in the cerebellar cortex; there are 25% fewer synapses compared to wild-type

abnormal synapse morphology ( J:192431 )

• selective loss of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepripionic acid (AMPA) receptors at corticothalamic synapses in inhibitory neurons of the nucleus reticularis thalamus

abnormal synaptic vesicle morphology ( J:116541 )

• presynaptic vesicles are less dense compared to wild-type

abnormal synaptic vesicle number ( J:116541 )

• presynaptic vesicles are reduced in number

• there are fewer docked vesicles and fewer vesicles adjacent to the active zone ready to dock in mutants than in wild-type

abnormal brain wave pattern ( J:91987 )

• saline-treated mutants display frequent abnormal polyspike discharges in the EEG; however, these do not correlate temporally with dyskinetic behaviors

• after nifedipine treatment, polyspike discharges are increased while reducing dyskinesia scores in mutants; an inverse relationship is observed

Genotype
MGI:3810419

hm3

• Allelic Composition: Cacng2^stg/Cacng2^stg
• Genetic Background: involves: A/J

nervous system

absence of AMPA-mediated synaptic currents ( J:163184 )

• mice lack the AMPA receptor component of the excitatory postsynaptic currents

abnormal miniature excitatory postsynaptic currents ( J:163184 )

• mice lack miniature excitatory postsynaptic current amplitudes

behavior/neurological

ataxia ( J:138791 )

growth/size/body

decreased body weight ( J:138791 )

• about 75% the weight of control littermates at P14

Genotype
MGI:3700749

hm4

• Allelic Composition: Cacng2^stg/Cacng2^stg
• Genetic Background: involves: A/J * C3HeB/FeJ * C57BL/6J

nervous system

nervous system phenotype ( J:121463 )

N • synaptic electrophysiology including neurotransmitter release and end plate potentials, as well as responses to channel inhibitors is not different from wild-type NMJs

abnormal motor neuron morphology ( J:121463 )

• fiber diameter at diaphragm NMJs (14.2 um) is slightly reduced compared with wild-type (15.8 um)

abnormal neuromuscular synapse morphology ( J:121463 )

• neuromuscular junction area (area staining for acetylcholine receptors) in ~25% smaller relative to wild-type mice (333 um² vs 446 um²)

abnormal CNS synaptic transmission ( J:106959 )

• peak current densities of low voltage-activated (LVA) calcium channels in thalamocortical neurons at membrane potential of -50 mV are increased by 45% compared to control

• peak current densities of high voltage calcium channels (HVA) in TC neurons are increased compared to wild-type

Genotype
MGI:3812002

hm5

• Allelic Composition: Cacng2^stg/Cacng2^stg
• Genetic Background: Not Specified

nervous system

reduced AMPA-mediated synaptic currents ( J:140010 )

• AMPAR mediated miniature excitatory post synaptic currents (mEPSC) in inhibitory nucleus reticularis (nRT) neurons are significantly reduced in frequency and amplitude in P14-17 mice

• amplitude, but not frequency, is decreased in older P21-23 mice although there are fewer events

• AMPAR mediated EPSCs frequency and amplitude are not significantly altered in excitatory relay neurons, with the exception that frequency is decreased in older mice

• ratio of AMPA to NMDA EPSCs is reduced by 50% in nRT neurons

• Purkinje cell climbing and parallel fiber synapses both exhibit a decrease in the ratio of stimulation intensity in AMPA to kainite receptor and mGlur-induced EPSCs(70% and 50% respectively)

Genotype
MGI:5307143

cx6

• Allelic Composition: Cacng2^stg/Cacng2^stg; Cacng8^tm1.1Suto/Cacng8^tm1.1Suto
• Genetic Background: involves: A/J

mortality/aging

premature death ( J:179775 )

• most die by P28

growth/size/body

postnatal growth retardation ( J:179775 )

• severe

Genotype
MGI:3810418

cx7

• Allelic Composition: Cacng2^stg/Cacng2^stg; Cacng3^tm1Ran/Cacng3^tm1Ran
• Genetic Background: involves: A/J

mortality/aging

postnatal lethality, incomplete penetrance ( J:138791 )

• most die by 2 weeks of age with few surviving beyond 4 weeks of age

behavior/neurological

ataxia ( J:138791 )

• more severe than in Cacng2^stg single homozygotes

nervous system

abnormal CNS synaptic transmission ( J:138791 )

• the I - V relationship of synaptic AMPA receptor mediated currents is inwardly rectified as opposed to linear as in controls

abnormal excitatory postsynaptic currents ( J:138791 )

• nearly a 90% reduction in compound EPSC is seen

abnormal miniature excitatory postsynaptic currents ( J:138791 )

• Golgi cell mEPSCs show about a 90% reduction in frequency and a large change in amplitude

• decay of mEPSCs is nearly twice as fast as in controls

growth/size/body

decreased body weight ( J:138791 )

• about 55% the weight of control littermates at P14

Genotype
MGI:3531476

cx8

• Allelic Composition: Cacng2^stg/Cacng2^stg; Cacng4^tm1Frk/Cacng4^tm1Frk
• Genetic Background: involves: B6C3Fe a/a-Cacng2^stg/J * B6.129-Cacng4^tm1Frk/J

mortality/aging

postnatal lethality, incomplete penetrance ( J:96506 )

• most mice that survive birth die before 4 weeks of age

prenatal lethality, incomplete penetrance ( J:96506 )

• incomplete penetrance; very few mutant mice survive to birth