vision/eye phenotype

• abnormal cornea morphology
  • at 8 months, around half of mutants may have serous exudate and or corneal lesions in one or both eyes
  (MGI Ref ID J:115694)

• corneal scarring
  • at 8 months, around half of mutants display a mild eye phenotype with corneal lesions and /or serous exudate in one or both eyes
  (MGI Ref ID J:115694)

behavior/neurological phenotype

• seizures
  • occur during both sleep and wakefulness
  (MGI Ref ID J:115694)

• ataxia
  • by 8 months of age, mice display ataxia
  (MGI Ref ID J:115694)

• myoclonus
  • mice display frequent spontaneous axial myoclonic jerks at rate of 10-15/hour; head and neck are always involved, with whole body involved in most animals
  (MGI Ref ID J:115694)

muscle phenotype

• myoclonus
  • mice display frequent spontaneous axial myoclonic jerks at rate of 10-15/hour; head and neck are always involved, with whole body involved in most animals
  (MGI Ref ID J:115694)

nervous system phenotype

• abnormal cerebellar granule cell morphology
  • widespread granule cell apoptosis is observed in mice at 2, 4, and 6 months of age
  (MGI Ref ID J:115694)

• abnormal brain wave pattern
  • baseline cortical activity displays normal low-amplitude desynchronized EEG with intermittent interictal discharges and bilateral electrographic seizure discharges
  (MGI Ref ID J:115694)

• seizures
  • occur during both sleep and wakefulness
  (MGI Ref ID J:115694)

• abnormal cerebellum morphology
  • apoptosis is observed in cerebellum of mutants but not in wild-type brain at 4 months
  (MGI Ref ID J:115694)

• myoclonus
  • mice display frequent spontaneous axial myoclonic jerks at rate of 10-15/hour; head and neck are always involved, with whole body involved in most animals
  (MGI Ref ID J:115694)

cellular phenotype

• abnormal apoptosis
  • notably, the cerebellum of pure 129X1/SvJ mutant mice contained ~2-fold more TUNEL-positive granule cells than age-matched mutants derived from the mixed 129Sv x C57BL/6 genetic background
  (MGI Ref ID J:50587)
  • ures, including the presence of apoptotic bodies and cytoplasmic vacuoles
  (MGI Ref ID J:50587)
  • at 3 months, TEM analysis of cerebellar tissue from pure 129X1/SvJ homozygous null mice revealed that granule cells showed both early apoptotic cellular features, including chromatin marginization and nuclear condensation, and late apoptotic cellular features, including the presence of apoptotic bodies and cytoplasmic vacuoles
  (MGI Ref ID J:50587)
  • in addition to the decreased density of granule cells, all homozygotes contained numerous TUNEL-positive apoptotic cells in the granule cell layer of the cerebellum, regardless of their age
  (MGI Ref ID J:50587)

immune system phenotype

• uveitis
  • a few corneal opacities were associated with anterior uveitis, i.e. accumulations of neutrophils in the anterior chamber
  (MGI Ref ID J:50587)

• increased incidence of corneal inflammation
  • with increasing age, increased incidence of corneal inflammation was observed in the absence of bacterial or viral infections
  (MGI Ref ID J:50587)

mammalian phenotype

• growth/size/body region phenotype
  • Normal - at 1-3 months of age, mutant mice displayed normal size and weight relative to wild-type
  (MGI Ref ID J:50587)
  • Normal - homozygous null mice were viable and appeared phenotypically normal at 3 weeks prior to weaning
  (MGI Ref ID J:50587)

• behavior/neurological phenotype
  • Normal - at 1-3 months of age, mutant mice displayed normal grooming behavior, coordination and strength
  (MGI Ref ID J:50587)

muscle phenotype

• myoclonus
  • each event lasted from a few seconds to several minutes, and ended with a large myoclonic outburst that catapulted the animal into the air
  (MGI Ref ID J:50587)
  • ECoG recordings from awake homozygotes, or mutant mice on the mixed 129Sv x C57BL/6 genetic background, showed no identifiable cortical seizure patterns
  (MGI Ref ID J:50587)
  • shaking became more prominent with intermittent lightning-like muscle jerks, sometimes propelling the animal forward
  (MGI Ref ID J:50587)
  • after the seizure, animals remained still for several seconds, and finally regained mobility
  (MGI Ref ID J:50587)
  • recordings revealed a bilaterally synchronous 4-6-Hz repetitive spike discharge which coincided with the onset of the hyperkinetic behaviour; ECoG activity reverted to the normal non-spiking pattern upon regaining mobility
  (MGI Ref ID J:50587)
  • during sleep, the entire myoclonic seizure occurred often, sometimes every several minutes; seizures occurred only during sleep
  (MGI Ref ID J:50587)
  • isogenic 129/Sv mutant mice developed myoclonus and seizures during sleep by 1 month of age
  (MGI Ref ID J:50587)
  • electrocortical graph recordings revealed abnormal cortical activity during the stereotyped behavioral seizures; seizure episodes correlated precisely (1:1) with the multifocal myoclonic activity
  (MGI Ref ID J:50587)
  • seizure episodes were typified by short twitching of either the whiskers, ears or tail, followed by facial spasms and minor shaking of the torso and limbs
  (MGI Ref ID J:50587)
  • isogenic 129/Sv mutant mice exhibited no photoconvulsive response following a 1-45-Hz photic stimulation
  (MGI Ref ID J:50587)

• facial muscle spasm
  (MGI Ref ID J:50587)

behavior/neurological phenotype

• impaired coordination
  • at 7-9 months of age, mutant mice performed poorly on both the still and rotating rotorod
  (MGI Ref ID J:50587)

• myoclonus
  • ECoG recordings from awake homozygotes, or mutant mice on the mixed 129Sv x C57BL/6 genetic background, showed no identifiable cortical seizure patterns
  (MGI Ref ID J:50587)
  • shaking became more prominent with intermittent lightning-like muscle jerks, sometimes propelling the animal forward
  (MGI Ref ID J:50587)
  • each event lasted from a few seconds to several minutes, and ended with a large myoclonic outburst that catapulted the animal into the air
  (MGI Ref ID J:50587)
  • electrocortical graph recordings revealed abnormal cortical activity during the stereotyped behavioral seizures; seizure episodes correlated precisely (1:1) with the multifocal myoclonic activity
  (MGI Ref ID J:50587)
  • seizure episodes were typified by short twitching of either the whiskers, ears or tail, followed by facial spasms and minor shaking of the torso and limbs
  (MGI Ref ID J:50587)
  • after the seizure, animals remained still for several seconds, and finally regained mobility
  (MGI Ref ID J:50587)
  • isogenic 129/Sv mutant mice exhibited no photoconvulsive response following a 1-45-Hz photic stimulation
  (MGI Ref ID J:50587)
  • during sleep, the entire myoclonic seizure occurred often, sometimes every several minutes; seizures occurred only during sleep
  (MGI Ref ID J:50587)
  • isogenic 129/Sv mutant mice developed myoclonus and seizures during sleep by 1 month of age
  (MGI Ref ID J:50587)
  • recordings revealed a bilaterally synchronous 4-6-Hz repetitive spike discharge which coincided with the onset of the hyperkinetic behaviour; ECoG activity reverted to the normal non-spiking pattern upon regaining mobility
  (MGI Ref ID J:50587)

• ataxia
  • at 6 months, homozygous null mice showed mild signs of ataxia
  (MGI Ref ID J:50587)

• abnormal gait
  • at >6 months, mutant mice walked with a wide-based gait and, upon hindlimb rearing, occasionally fell on their sides, but still displayed normal swimming ability
  (MGI Ref ID J:50587)

nervous system phenotype

• myoclonus
  • during sleep, the entire myoclonic seizure occurred often, sometimes every several minutes; seizures occurred only during sleep
  (MGI Ref ID J:50587)
  • isogenic 129/Sv mutant mice developed myoclonus and seizures during sleep by 1 month of age
  (MGI Ref ID J:50587)
  • seizure episodes were typified by short twitching of either the whiskers, ears or tail, followed by facial spasms and minor shaking of the torso and limbs
  (MGI Ref ID J:50587)
  • shaking became more prominent with intermittent lightning-like muscle jerks, sometimes propelling the animal forward
  (MGI Ref ID J:50587)
  • after the seizure, animals remained still for several seconds, and finally regained mobility
  (MGI Ref ID J:50587)
  • ECoG recordings from awake homozygotes, or mutant mice on the mixed 129Sv x C57BL/6 genetic background, showed no identifiable cortical seizure patterns
  (MGI Ref ID J:50587)
  • each event lasted from a few seconds to several minutes, and ended with a large myoclonic outburst that catapulted the animal into the air
  (MGI Ref ID J:50587)
  • electrocortical graph recordings revealed abnormal cortical activity during the stereotyped behavioral seizures; seizure episodes correlated precisely (1:1) with the multifocal myoclonic activity
  (MGI Ref ID J:50587)
  • recordings revealed a bilaterally synchronous 4-6-Hz repetitive spike discharge which coincided with the onset of the hyperkinetic behaviour; ECoG activity reverted to the normal non-spiking pattern upon regaining mobility
  (MGI Ref ID J:50587)
  • isogenic 129/Sv mutant mice exhibited no photoconvulsive response following a 1-45-Hz photic stimulation
  (MGI Ref ID J:50587)

• abnormal nervous system physiology
  • quantitative RT-PCR revealed significant increases in the transcript levels of several transcripts in neurological tissues from inbred 129X1/SvJ homozygous null mice
  (MGI Ref ID J:71823)

• cerebellum hypoplasia
  • at 6-9 months, older homozygous null mice displayed a reduction in the density of the granule cell layer in the cerebellum
  (MGI Ref ID J:50587)

vision/eye phenotype

• abnormal cornea morphology
  • the corneal epithelial layers appeared eroded, ulcerated, or hyperplastic and keratinized
  (MGI Ref ID J:50587)

• increased incidence of corneal inflammation
  • with increasing age, increased incidence of corneal inflammation was observed in the absence of bacterial or viral infections
  (MGI Ref ID J:50587)

• corneal opacity
  • as homozygous null mice aged from 3 to 7 months, 35% of mutants and 0% of wild-type littermates developed corneal opacity in one or both eyes; in 35% of the cases, both eyes were affected
  (MGI Ref ID J:50587)
  • corneal opacities corresponded with histopathological lesions of acute to chronic keratitis
  (MGI Ref ID J:50587)

• uveitis
  • a few corneal opacities were associated with anterior uveitis, i.e. accumulations of neutrophils in the anterior chamber
  (MGI Ref ID J:50587)

• abnormal eye physiology
  • at 1-3 months of age, approximately 40% of homozygous null mice displayed narrowed palpebral fissures (squinting), increased lacrimation (tearing) and periocular buildup of serous to mucoid exudate
  (MGI Ref ID J:50587)