Mouse Genome Informatics
hm1
    Cstbtm1Rm/Cstbtm1Rm
either: (involves: 129S1/Sv * 129X1/SvJ) or (involves: 129S1/Sv * 129X1/SvJ * C57BL/6)
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
N
• at 1-3 months of age, mutant mice displayed normal grooming behavior, coordination and strength (J:50587)
• at 6 months, homozygous null mice showed mild signs of ataxia
• at 7-9 months of age, mutant mice performed poorly on both the still and rotating rotorod
• 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
• isogenic 129/Sv mutant mice developed myoclonus and seizures during sleep by 1 month of age
• 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
• shaking became more prominent with intermittent lightning-like muscle jerks, sometimes propelling the animal forward
• each event lasted from a few seconds to several minutes, and ended with a large myoclonic outburst that catapulted the animal into the air
• after the seizure, animals remained still for several seconds, and finally regained mobility
• during sleep, the entire myoclonic seizure occurred often, sometimes every several minutes; seizures occurred only during sleep
• electrocortical graph recordings revealed abnormal cortical activity during the stereotyped behavioral seizures; seizure episodes correlated precisely (1:1) with the multifocal myoclonic activity
• 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
• isogenic 129/Sv mutant mice exhibited no photoconvulsive response following a 1-45-Hz photic stimulation
• ECoG recordings from awake homozygotes, or mutant mice on the mixed 129Sv x C57BL/6 genetic background, showed no identifiable cortical seizure patterns

cellular
• 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
• 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
• 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

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

immune system
• with increasing age, increased incidence of corneal inflammation was observed in the absence of bacterial or viral infections
• a few corneal opacities were associated with anterior uveitis, i.e. accumulations of neutrophils in the anterior chamber

muscle
• isogenic 129/Sv mutant mice developed myoclonus and seizures during sleep by 1 month of age
• 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
• shaking became more prominent with intermittent lightning-like muscle jerks, sometimes propelling the animal forward
• each event lasted from a few seconds to several minutes, and ended with a large myoclonic outburst that catapulted the animal into the air
• after the seizure, animals remained still for several seconds, and finally regained mobility
• during sleep, the entire myoclonic seizure occurred often, sometimes every several minutes; seizures occurred only during sleep
• electrocortical graph recordings revealed abnormal cortical activity during the stereotyped behavioral seizures; seizure episodes correlated precisely (1:1) with the multifocal myoclonic activity
• 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
• isogenic 129/Sv mutant mice exhibited no photoconvulsive response following a 1-45-Hz photic stimulation
• ECoG recordings from awake homozygotes, or mutant mice on the mixed 129Sv x C57BL/6 genetic background, showed no identifiable cortical seizure patterns

vision/eye
• the corneal epithelial layers appeared eroded, ulcerated, or hyperplastic and keratinized
• 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
• corneal opacities corresponded with histopathological lesions of acute to chronic keratitis
• 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
• with increasing age, increased incidence of corneal inflammation was observed in the absence of bacterial or viral infections
• a few corneal opacities were associated with anterior uveitis, i.e. accumulations of neutrophils in the anterior chamber

nervous system
• at 6-9 months, older homozygous null mice displayed a reduction in the density of the granule cell layer in the cerebellum
• quantitative RT-PCR revealed significant increases in the transcript levels of several transcripts in neurological tissues from inbred 129X1/SvJ homozygous null mice
• isogenic 129/Sv mutant mice developed myoclonus and seizures during sleep by 1 month of age
• 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
• shaking became more prominent with intermittent lightning-like muscle jerks, sometimes propelling the animal forward
• each event lasted from a few seconds to several minutes, and ended with a large myoclonic outburst that catapulted the animal into the air
• after the seizure, animals remained still for several seconds, and finally regained mobility
• during sleep, the entire myoclonic seizure occurred often, sometimes every several minutes; seizures occurred only during sleep
• electrocortical graph recordings revealed abnormal cortical activity during the stereotyped behavioral seizures; seizure episodes correlated precisely (1:1) with the multifocal myoclonic activity
• 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
• isogenic 129/Sv mutant mice exhibited no photoconvulsive response following a 1-45-Hz photic stimulation
• ECoG recordings from awake homozygotes, or mutant mice on the mixed 129Sv x C57BL/6 genetic background, showed no identifiable cortical seizure patterns

Mouse Models of Human Disease
OMIM IDRef(s)
Myoclonic Epilepsy of Unverricht and Lundborg 254800 J:50587 , J:71823


Mouse Genome Informatics
hm2
    Cstbtm1Rm/Cstbtm1Rm
involves: 129S1/Sv * 129X1/SvJ * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• by 8 months of age, mice display ataxia
• occur during both sleep and wakefulness
• 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

nervous system
• occur during both sleep and wakefulness
• 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
• apoptosis is observed in cerebellum of mutants but not in wild-type brain at 4 months
• widespread granule cell apoptosis is observed in mice at 2, 4, and 6 months of age
• baseline cortical activity displays normal low-amplitude desynchronized EEG with intermittent interictal discharges and bilateral electrographic seizure discharges

vision/eye
• at 8 months, around half of mutants may have serous exudate and or corneal lesions in one or both eyes
• at 8 months, around half of mutants display a mild eye phenotype with corneal lesions and /or serous exudate in one or both eyes

muscle
• 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


Mouse Genome Informatics
cx3
    Bidtm1Sjk/Bidtm1Sjk
Cstbtm1Rm/Cstbtm1Rm

involves: 129S1/Sv * 129X1/SvJ * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• by 8 months of age, mice display ataxia; severity is similar to that of Cstb-single null mice
• 4occur during both sleep and wakefulness
• 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

nervous system
• 4occur during both sleep and wakefulness
• 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
• widespread granule cell apoptosis is observed in mice at 2, 4, and 6 months of age, similar to Cstb-single null animals
• baseline cortical activity displays normal low-amplitude desynchronized EEG with intermittent interictal discharges and bilateral electrographic seizure discharges

vision/eye
• at 8 months, around two-thirds of mutants may have serous exudate in one or both eyes, similar to Cstb-null mice
• at 8 months, around two-thirds of mutants display a mild eye phenotype with corneal lesions, similar to Cstb-null mice

muscle
• 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