Phenotypes associated with this allele
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Kcna1tm1Tem mutation
(1 available);
any
Kcna1 mutation
(26 available)
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behavior/neurological
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• mutants display greater pain behavior in response to formalin injection; total paw licking time is greater in mutants
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• effects of subcutaneous morphine is attenuated in mutants compared to wild-type, as assessed by increase in latency in the thermal pain assays
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• mutant animals show reduced latencies in 2 thermal pain assays; in response to a focused light beam on the hind paw and in a hot plate assay, mutants more quickly display a paw flick or paw lick, respectively
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• mice develop seizures by P21
• mice treated with AATP (combination treatment of ascorbic acid, alpha-tocopherol and sodium pyruvate) show reduced seizure burden
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nervous system
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• mice develop seizures by P21
• mice treated with AATP (combination treatment of ascorbic acid, alpha-tocopherol and sodium pyruvate) show reduced seizure burden
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• low voltage activated K+ currents are significantly smaller than controls
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• action potentials are generated to very small current clamp steps
• threshold about 48 pA as opposed to 90pA for controls
• two times as many action potentials generated as by controls
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• paired-pulse ratios are 51% lower at the mossy fiber-CA3 synapses following paired-pulse stimulations and field potential slopes are about 225% larger than in wild-type mice
• mice treated with AATP show improved mossy fiber CA3-paired pulse ratios but does not influence the field potential slopes
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cellular
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• mice show reduced mitochondrial respiratory complex I respiratory rates: ATP-producing state III respiration is diminished by 32% in cortical and 36% in hippocampal mitochondria and the maximal rate of the electron transport (state V) is reduced in both cortical and hippocampal mitochondria, indicating that mitochondria consume less oxygen
• UCP2 protein levels are reduced by 20% in mitochondria and functional uncoupling is reduced by 68%, indicating a loss of function of the protein machinery that promotes successful electron transport
• mice treated with AATP show improved mitochondrial functions
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• the reduced mitochondrial respiratory complex I-driven respiratory rates are associated with a 20% increase in hydrogen peroxide levels in the cortex and a 35% increase in the hippocampus, indicating an elevation of reactive oxygen species (ROS) is mitochondria
• mice treated with AATP show a reduction of ROS by 14% in the hippocampus
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Kcna1tm1Tem mutation
(1 available);
any
Kcna1 mutation
(26 available)
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mortality/aging
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• die beginning at 2-3 weeks of age
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• die beginning at 2-3 weeks of age
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behavior/neurological
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• develop epilepsy
• seizures exacerbate cardiac abnormalities
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• myoclonus that corresponds to prolonged bradycardia
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cardiovascular system
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• mice exhibit interictal cardiac abnormalities
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• prolonged bradycardia, with extended periods of sinus bradycardia lasting many minutes
• however, overall basal heart rate is similar to wild-type, although the heart rate is more variable than in controls
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• excessive premature ventricular contractions
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• mice exhibit multiple patterns of functional cardiac rhythm disturbances
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• 5-fold increase in AV conduction blocks compared to controls
• most common AV block is type I, second-degree block characterized by a PR interval that progressively lengthened until the QRS complex was dropped
• less often, type 2, second-degree blocks are seen in which the heart skipped one or more beats without obvious PR lengthening
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muscle
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• myoclonus that corresponds to prolonged bradycardia
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nervous system
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• develop epilepsy
• seizures exacerbate cardiac abnormalities
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• myoclonus that corresponds to prolonged bradycardia
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Kcna1tm1Tem mutation
(1 available);
any
Kcna1 mutation
(26 available)
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nervous system
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• 2/3 show class IV seizures and half of those show class V seizures
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• enlarged ventral cortex in 69% of brains
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behavior/neurological
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• body tremors
• jittering
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• 2/3 show class IV seizures and half of those show class V seizures
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hearing/vestibular/ear
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• abnormal audiosensitivity
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• crusting in the outer ear
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vision/eye
homeostasis/metabolism
immune system
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• crusting in the outer ear
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Kcna1tm1Tem mutation
(1 available);
any
Kcna1 mutation
(26 available)
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behavior/neurological
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• after the swim test, mutants fall over and all limbs undergo violent tremors; tremors lessen as time progresses
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• mutants exhibit ataxic movemensts as they begin to walk following swim test recovery
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• mutants removed from the cold water bath after the swim test and placed on a dry platform fall onto their sides and show severe myotonia
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• in cold water at the end of a 2 minute period, mutant mice start to have difficulties in maintaining axial orientation while wild-type controls are unaffected
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• after the swim test, one mutant showed epileptic neural activity 7 minutes after the swim
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nervous system
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• after the swim test, one mutant showed epileptic neural activity 7 minutes after the swim
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• upon cooling of phrenic nerve-diaphragm preparations, the mutant preparation exhibits delayed repetitive discharge after a single nerve stimulation
(hyperexcitability) ; the wild-type NM transmission remains one-to-one irrespective of temperature
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Kcna1tm1Tem mutation
(1 available);
any
Kcna1 mutation
(26 available)
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mortality/aging
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• 50% of mice die suddenly between the third and fifth week of life
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nervous system
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• some mice exhibit seizures prior to dying
• mice that survive beyond 5 weeks of age exhibit spontaneous seizures lasting 20 seconds to 2 minutes once or twice an hour
• ictal behaviors include circling, facial clonus, rearing and falling, bilateral and alternating forelimb or hindlimb clonus or both and generalized tonic-clonic episodes
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• exposure to flurothyl induces seizure at a latency of 1.48+/-0.18 minutes (a 60% reduction compared to wild-type mice, 3.72+/.-0.07 minutes)
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• compound action potential is slower to repolarize that in wild-type mice
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• mice exhibit ictal electrocortical patterns that are usually associated with ictal behaviors
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• 21% of mossy fiber cells elicit a late burst discharge when stimulated that is not observed in wild-type cells
• the threshold for eliciting antidronic spike invasion is decreased (10.9+/-1.5 uA compared to 18.5+/-2.9 uA in wild-type CA3 pyramidal cells)
• however, initial fast excitatory postsynaptic potential, fast inhibitory postsynaptic potential and slow inhibitory postsynptical potential are normal
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• the refractory period in the sciatic nerve is increased after the second pulse
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behavior/neurological
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• during postnatal week 3, mice exhibit episodic eye blinking, twitching of vibrissiae, forelimb padding, arrested motion, and hyperstartle response
• ictal behaviors include circling, facial clonus, rearing and falling, bilateral and alternating forelimb or hindlimb clonus or both and generalized tonic-clonic episodes
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• during postnatal week 3
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• during postnatal week 3
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• some mice exhibit seizures prior to dying
• mice that survive beyond 5 weeks of age exhibit spontaneous seizures lasting 20 seconds to 2 minutes once or twice an hour
• ictal behaviors include circling, facial clonus, rearing and falling, bilateral and alternating forelimb or hindlimb clonus or both and generalized tonic-clonic episodes
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• exposure to flurothyl induces seizure at a latency of 1.48+/-0.18 minutes (a 60% reduction compared to wild-type mice, 3.72+/.-0.07 minutes)
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Allelic
Composition |
Kcna1tm1Tem/Kcna1+
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Genetic
Background |
involves: 129S7/SvEvBrd * various |
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Kcna1tm1Tem mutation
(1 available);
any
Kcna1 mutation
(26 available)
|
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nervous system
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• exposure to flurothyl induces seizure at a latency of 3.39+/-0.08 minutes (a 9% reduction compared to wild-type mice, 3.72+/.-0.07 minutes)
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behavior/neurological
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• exposure to flurothyl induces seizure at a latency of 3.39+/-0.08 minutes (a 9% reduction compared to wild-type mice, 3.72+/.-0.07 minutes)
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Analysis Tools