Phenotypes associated with this allele

• Allele Symbol: Kcna1^tm1Tem
• Allele Name: targeted mutation 1, Bruce L Tempel
• Allele ID: MGI:1861959
• Summary: 6 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Kcna1^tm1Tem/Kcna1^tm1Tem	C3Fe.129S7-Kcna1^tm1Tem	MGI:3625870
hm2	Kcna1^tm1Tem/Kcna1^tm1Tem	involves: 129S7/SvEvBrd	MGI:4833820
hm3	Kcna1^tm1Tem/Kcna1^tm1Tem	involves: 129S7/SvEvBrd * BALB/cByJ * C3HeB/FeJ	MGI:3770609
hm4	Kcna1^tm1Tem/Kcna1^tm1Tem	involves: 129S7/SvEvBrd * C57BL/6	MGI:3625906
hm5	Kcna1^tm1Tem/Kcna1^tm1Tem	involves: 129S7/SvEvBrd * various	MGI:2181401
ht6	Kcna1^tm1Tem/Kcna1^+	involves: 129S7/SvEvBrd * various	MGI:3770444

Genotype
MGI:3625870

hm1

• Allelic Composition: Kcna1^tm1Tem/Kcna1^tm1Tem
• Genetic Background: C3Fe.129S7-Kcna1^tm1Tem

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

behavior/neurological

decreased chemical nociceptive threshold ( J:107933 )

• mutants display greater pain behavior in response to formalin injection; total paw licking time is greater in mutants

decreased chemically-elicited antinociception ( J:107933 )

• effects of subcutaneous morphine is attenuated in mutants compared to wild-type, as assessed by increase in latency in the thermal pain assays

decreased thermal nociceptive threshold ( J:107933 )

• 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

seizures ( J:206598 )

• mice develop seizures by P21

• mice treated with AATP (combination treatment of ascorbic acid, alpha-tocopherol and sodium pyruvate) show reduced seizure burden

nervous system

seizures ( J:206598 )

• mice develop seizures by P21

• mice treated with AATP (combination treatment of ascorbic acid, alpha-tocopherol and sodium pyruvate) show reduced seizure burden

abnormal nervous system electrophysiology ( J:105296 )

• low voltage activated K+ currents are significantly smaller than controls

abnormal action potential ( J:105296 )

• 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

decreased nerve fiber response threshold ( J:105296 )

decreased paired-pulse ratio ( J:206598 )

• 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

cellular

abnormal mitochondrial ATP synthesis coupled electron transport ( J:206598 )

• 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

oxidative stress ( J:206598 )

• 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

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
temporal lobe epilepsy		DOID:3328	OMIM:PS600512	J:206598

Genotype
MGI:4833820

hm2

• Allelic Composition: Kcna1^tm1Tem/Kcna1^tm1Tem
• Genetic Background: involves: 129S7/SvEvBrd

mortality/aging

premature death ( J:164091 )

• die beginning at 2-3 weeks of age

postnatal lethality, incomplete penetrance ( J:164091 )

• die beginning at 2-3 weeks of age

behavior/neurological

seizures ( J:164091 )

• develop epilepsy

• seizures exacerbate cardiac abnormalities

myoclonus ( J:164091 )

• myoclonus that corresponds to prolonged bradycardia

tonic-clonic seizures ( J:164091 )

cardiovascular system

abnormal cardiovascular system physiology ( J:164091 )

• mice exhibit interictal cardiac abnormalities

decreased heart rate ( J:164091 )

• 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

ventricular premature beat ( J:164091 )

• excessive premature ventricular contractions

abnormal impulse conducting system conduction ( J:164091 )

• mice exhibit multiple patterns of functional cardiac rhythm disturbances

atrioventricular block ( J:164091 )

• 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

muscle

myoclonus ( J:164091 )

• myoclonus that corresponds to prolonged bradycardia

nervous system

seizures ( J:164091 )

• develop epilepsy

• seizures exacerbate cardiac abnormalities

myoclonus ( J:164091 )

• myoclonus that corresponds to prolonged bradycardia

tonic-clonic seizures ( J:164091 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
epilepsy		DOID:1826		J:164091

Genotype
MGI:3770609

hm3

• Allelic Composition: Kcna1^tm1Tem/Kcna1^tm1Tem
• Genetic Background: involves: 129S7/SvEvBrd * BALB/cByJ * C3HeB/FeJ

nervous system

convulsive seizures ( J:119491 )

• 2/3 show class IV seizures and half of those show class V seizures

enlarged hippocampus ( J:119491 )

• in 69% of brains

abnormal cerebral cortex morphology ( J:119491 )

• enlarged ventral cortex in 69% of brains

behavior/neurological

increased startle reflex ( J:119491 )

• hyperstartle response

tremors ( J:119491 )

• body tremors

• jittering

abnormal posture ( J:119491 )

abnormal locomotor behavior ( J:119491 )

• abnormal limb paddling

convulsive seizures ( J:119491 )

• 2/3 show class IV seizures and half of those show class V seizures

hearing/vestibular/ear

abnormal hearing physiology ( J:119491 )

• abnormal audiosensitivity

ear inflammation ( J:119491 )

• crusting in the outer ear

vision/eye

eye inflammation ( J:119491 )

• crusting of the eyelid

homeostasis/metabolism

porphyria ( J:119491 )

immune system

ear inflammation ( J:119491 )

• crusting in the outer ear

eye inflammation ( J:119491 )

• crusting of the eyelid

Genotype
MGI:3625906

hm4

• Allelic Composition: Kcna1^tm1Tem/Kcna1^tm1Tem
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6

behavior/neurological

tremors ( J:77281 )

• after the swim test, mutants fall over and all limbs undergo violent tremors; tremors lessen as time progresses

ataxia ( J:77281 )

• mutants exhibit ataxic movemensts as they begin to walk following swim test recovery

impaired balance ( J:77281 )

• 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

impaired swimming ( J:77281 )

• 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

seizures ( J:77281 )

• after the swim test, one mutant showed epileptic neural activity 7 minutes after the swim

nervous system

seizures ( J:77281 )

• after the swim test, one mutant showed epileptic neural activity 7 minutes after the swim

abnormal PNS synaptic transmission ( J:77281 )

• 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

Genotype
MGI:2181401

hm5

• Allelic Composition: Kcna1^tm1Tem/Kcna1^tm1Tem
• Genetic Background: involves: 129S7/SvEvBrd * various

mortality/aging

premature death ( J:47349 )

• 50% of mice die suddenly between the third and fifth week of life

nervous system

seizures ( J:47349 )

• 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

increased susceptibility to pharmacologically induced seizures ( J:47349 )

• 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)

tonic-clonic seizures ( J:47349 )

abnormal action potential ( J:47349 )

• compound action potential is slower to repolarize that in wild-type mice

abnormal brain wave pattern ( J:47349 )

• mice exhibit ictal electrocortical patterns that are usually associated with ictal behaviors

abnormal CNS synaptic transmission ( J:47349 )

• 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

abnormal paired-pulse facilitation ( J:47349 )

• the refractory period in the sciatic nerve is increased after the second pulse

behavior/neurological

abnormal behavior ( J:47349 )

• 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

increased blinking frequency ( J:47349 )

• during postnatal week 3

increased startle reflex ( J:47349 )

• during postnatal week 3

seizures ( J:47349 )

• 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

increased susceptibility to pharmacologically induced seizures ( J:47349 )

• 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)

tonic-clonic seizures ( J:47349 )

Genotype
MGI:3770444

ht6

• Allelic Composition: Kcna1^tm1Tem/Kcna1⁺
• Genetic Background: involves: 129S7/SvEvBrd * various

nervous system

increased susceptibility to pharmacologically induced seizures ( J:47349 )

• 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)

behavior/neurological

increased susceptibility to pharmacologically induced seizures ( J:47349 )

• 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)