Analysis Tools
mortality/aging
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• mice exhibit reduced life span, with a median survival of 43 days
• adult mice treated with an intracerebroventricular bolus injection of a Kcnt1-silencing antisense oligonucleotide (ASO) show an increase in survival
• Kcnt1-ASO administration at neonatal age extends life span, with first deaths observed at P135 and showing approximately 25% mortality by P150
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• only 8.8% of pups born are homozygotes by age P8-P12, indicating some early lethality
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growth/size/body
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• mice are smaller
• Kcnt1-ASO administration at neonatal age increases body weight but mice are still smaller than wild-type mice
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behavior/neurological
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• mice are prone to anxiety-like traits in the light/dark box test, spending less time in the light chamber
• administration of Kcnt1-ASO has no effect on behavior in the light/dark box test
• however, no differences in social behaviors are seen in the 3-chamber social interaction test and Y maze test
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• mice show a preference for the open arms in the elevated plus maze, suggesting reduced fear of open and elevated spaces
• adult and neonatal mice administered Kcnt1-ASO show a reduction in the time spent on the open arms
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• mice show a tendency toward hyperactive exploratory behavior in the locomotor cells test, especially within the first 20 minutes of testing
• adult and neonatal mice administered Kcnt1-ASO show reduced exploratory behavior
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• nesting behavior is impaired at P40
• adult or neonatal aged mice administered Kcnt1-ASO show an in improvement in nesting behavior
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• spontaneous tonic-clonic seizures are seen as early as P18
• diverse seizure phenotypes are seen, with milder seizures lasting approximately 1-2 min and involving clonic movements of the forelimbs, neck, and head while in a seated posture and mores severe seizures that include generalized tonic-clonic episodes with Straub tail, wild running and jumping, loss of postural tone, and tonic hind limb extension
• status epilepticus is also seen and in most cases results in death
• the frequency of tonic-clonic seizures is variable
• electrocorticogram (ECoG) recordings show the presence of frequent high-amplitude interictal acute spikes
• convulsive seizures are associated with ictal ECoG signals characterized by clusters of high-amplitude sharp-wave activity followed by electrical suppression at the end of the seizure
• adult symptomatic mice treated with an intracerebroventricular bolus injection of a Kcnt1-silencing antisense oligonucleotide show reduced seizure frequency
• Kcnt1-ASO administration at neonatal age is effective at reducing seizure frequency
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nervous system
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• spontaneous tonic-clonic seizures are seen as early as P18
• diverse seizure phenotypes are seen, with milder seizures lasting approximately 1-2 min and involving clonic movements of the forelimbs, neck, and head while in a seated posture and mores severe seizures that include generalized tonic-clonic episodes with Straub tail, wild running and jumping, loss of postural tone, and tonic hind limb extension
• status epilepticus is also seen and in most cases results in death
• the frequency of tonic-clonic seizures is variable
• electrocorticogram (ECoG) recordings show the presence of frequent high-amplitude interictal acute spikes
• convulsive seizures are associated with ictal ECoG signals characterized by clusters of high-amplitude sharp-wave activity followed by electrical suppression at the end of the seizure
• adult symptomatic mice treated with an intracerebroventricular bolus injection of a Kcnt1-silencing antisense oligonucleotide show reduced seizure frequency
• Kcnt1-ASO administration at neonatal age is effective at reducing seizure frequency
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| developmental and epileptic encephalopathy 14 | DOID:0080439 |
OMIM:614959 |
J:333512 | |
