Overview

This targeted mutation of the potassium voltage-gated channel, shaker-related subfamily, member 2 (Kcna2) gene exhibits spontaneous seizures may be useful in studies of voltage dependent potassium channels and epilepsy.

Donating Investigator

Dr. Bruce L. Tempel, Univ of Washington School of Medicine

Genetic overview

Genetic Background	Generation

Kcna2^tm1Tem

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Kcna2	potassium voltage-gated channel, shaker-related subfamily, member 2

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Research Applications

Neurobiology Research
Developmental Biology Research
Cell Biology Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

Homozygous mice appear normal at birth, however, by day 15 mice are smaller and exhibit explosive running and bouncing seizures sometimes followed by tonic extension accompanied by a shortness of breath (apnea). These seizures occur at a rate of less than one per day and have a 50% fatality rate. Mean lifespan is approximately 17 days on both the mixed C57BL/6-129S7 background and the C3H background. In homozygous mice, auditory neurons of the medial nucleus of the trapezoid body (MNTB) exhibit a decrease in action potential firing (hypoexcitable) and higher threshold current amplitude than wild-type mice. MNTB neurons in heterozygous mice exhibit an intermediate phenotype. The counter-intuitive decrease in activity with the deletion of Kv1.2 subunits occurs because replacement subunits (most likely Kv1.1) are lower-threshold than Kv1.2. This mutant mouse strain may be useful in studies of voltage dependent potassium channels and epilepsy.

In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.

Development

A targeting vector containing the neomycin resistance gene was used to replace the open reading frame of the targeted gene. The construct was electroporated into 129S7/SvEvTac derived AB1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. The resulting chimeric animals were crossed to C3HeB/FeJ and backcrossed for greater than 30 generations. In 2008, as a result of breeding difficulties, the strain was backcrossed to CBA/CaJ for 2 generations. Upon arrival, mice were bred to C3HeB/FeJ for at least 1 generation to establish the colony.

Control Suggestions

Wild-type from the colony

Additional Information

Considerations for Choosing Controls

Selected References

Brew HM; Gittelman JX; Silverstein RS; Hanks TD; Demas VP; Robinson LC; Robbins CA; McKee-Johnson J; Chiu SY; Messing A; Tempel BL. 2007. Seizures and reduced life span in mice lacking the potassium channel subunit Kv1.2, but hypoexcitability and enlarged Kv1 currents in auditory neurons. J Neurophysiol 98(3):1501-25PubMed: 17634333 MGI: J:131735

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Genetics

Kcna2^tm1Tem

Allele Symbol: Kcna2^tm1Tem

Allele Name	targeted mutation 1, Bruce L Tempel
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)
Gene Symbol and Name	Kcna2, potassium voltage-gated channel, shaker-related subfamily, member 2
Gene Synonym(s)
Strain of Origin	129S7/SvEvBrd-Hprt⁺
Chromosome	3
Molecular Note	A neomycin resistance cassette replaced the entire open reading frame. mRNAQ cannot be found by quantitative PCR and protein product cannot be identified by Western blot in extracts from homozygous mutant mice.
Mutations Made By	Dr. Bruce Tempel, Univ of Washington School of Medicine

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Neurobiology Research
- Epilepsy
- Channel and Transporter Defects
  - potassium
Developmental Biology Research
- Postnatal Lethality
  - Homozygous
Cell Biology Research
- Channel and Transporter Defects
  - potassium

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Kcna2^tm1Tem/Kcna2^tm1Tem
C3Fe.129S7-Kcna2

nervous system phenotype

abnormal channel response
- voltage-clamped inwards rectifier potassium current is larger than in wild-type neurons

abnormal nervous system electrophysiology
- Normal - however, treatment with dendrotoxin abolishes the differences in neuron electrophysiology compared to wild-type neurons
- tityustoxin has no effect on neurons electrophysiology unlike in wild-type mice
- neurons exhibit less depolarized sustained membrane potentials and reduced mean resting input resistance compared to wild-type neurons

impaired ability to fire action potentials
- neurons hypoexcitability does not change depending on the age of mice
- neurons fire one action potentials when stimulated with 200-pA compared to 3 fired by wild-type mice

tonic seizures
- observed seizure fatality rate is 50% and does not increased with age
- mice exhibit bursts of wild running and jumping followed by 5 to 10 seconds of full tonic extension similar to running bouncing seizures (RBS)

abnormal action potential
- Normal - however, all other action potentials and properties not dependent on potassium signaling are normal
- neurons exhibit a higher amplitude threshold than wild-type or heterozygous mice
- almost all neurons have low excitability compared to wild-type neurons

increased susceptibility to pharmacologically induced seizures
- mice exhibit a shorter latency to seizure following treatment with flurothyl compared to wild-type mice and heterozygotes
- latency to running bouncing seizures is 40% less than in wild-type mice or heterozygotes

behavior/neurological phenotype

increased susceptibility to pharmacologically induced seizures
- mice exhibit a shorter latency to seizure following treatment with flurothyl compared to wild-type mice and heterozygotes
- latency to running bouncing seizures is 40% less than in wild-type mice or heterozygotes

tonic seizures
- mice exhibit bursts of wild running and jumping followed by 5 to 10 seconds of full tonic extension similar to running bouncing seizures (RBS)
- observed seizure fatality rate is 50% and does not increased with age

respiratory system phenotype

apnea
- mice likely die due to apnea during tonic extension

growth/size/body region phenotype

decreased body weight
- at P14, mice weigh 1 g less than wild-type and heterozygous mice

mortality/aging

postnatal lethality, complete penetrance
- mice survive 17+/-2 days and likely die due to apnea during tonic extension
- observed seizure fatality rate is 50% and does not increased with age

Genotype: Kcna2^tm1Tem/Kcna2^tm1Tem
involves: 129S7/SvEvBrd

mortality/aging

postnatal lethality, complete penetrance
- mice exhibit seizures resulting in death by P28

nervous system phenotype

abnormal brain wave pattern
- during non rapid eye movement sleep, mice exhibit higher EEG power in the low-frequency range (0.5 to 1.0 Hz) and lower EEG power in the 3.5 to 7 Hz frequency compared to wild-type mice
- during seizures mice exhibit an ictal electroencephalography (EEG) pattern and abnormal spiking EEG activity

seizures
- during seizures mice exhibit an ictal electroencephalography (EEG) pattern and abnormal spiking EEG activity
- mice exhibit seizures resulting in death by P28
- seizures are rare at P17
- seizures occur during waking or during rapid eye movement sleep

behavior/neurological phenotype

seizures
- during seizures mice exhibit an ictal electroencephalography (EEG) pattern and abnormal spiking EEG activity
- mice exhibit seizures resulting in death by P28
- seizures occur during waking or during rapid eye movement sleep
- seizures are rare at P17

abnormal sleep pattern
- at P17, mice spend 23% less time in non-rapid eye movement (NREM) sleep, 21% more time in waking and a 10% decrease in rapid eye movement sleep (REM)compared to wild-type mice
- while the number of episodes of NREM are normal, the duration of NREM is reduced compared to in wild-type mice
- mice spend more time in waking during the light phase wild-type and heterozygous mice
- at P19, two mice exhibiting similar brain wave patterns as seen at P17 exhibit a 19% and 15% increase in waking time per 24 hours compared to wild-type and heterozygotes, respectively, and a 30% and 28% decrease in NREM sleep per 24 hours

growth/size/body region phenotype

decreased body size
- while normal for the first 2 weeks of life, by P16 mice are smaller than wild-type

Genotype: Kcna2^tm1Tem/Kcna2⁺
C3Fe.129S7-Kcna2

behavior/neurological phenotype

increased susceptibility to pharmacologically induced seizures
- mice exhibit a shorter latency to seizure following treatment with flurothyl compared to wild-type mice but not as short as in homozygotes

nervous system phenotype

impaired ability to fire action potentials
- neurons fire fewer action potentials than wild-type mice
- neurons hypoexcitability does not change depending on the age of mice

increased susceptibility to pharmacologically induced seizures
- mice exhibit a shorter latency to seizure following treatment with flurothyl compared to wild-type mice but not as short as in homozygotes

Genotype: Kcna2^tm1Tem/Kcna2^tm1Tem
involves: 129S7/SvEvBrd * C57BL/6

behavior/neurological phenotype

tonic seizures
- observed seizure fatality rate does not increased with age
- mice exhibit bursts of wild running and jumping followed by 5 to 10 seconds of full tonic extension similar to running bouncing seizures (RBS)

mammalian phenotype

behavior/neurological phenotype
- Normal - unlike mice homozygous for a null allele of Kcna1, mice do not exhibit hyperexcitability following a cold swim

mortality/aging

postnatal lethality, complete penetrance
- mice survive 17+/-2 days
- observed seizure fatality rate does not increased with age

nervous system phenotype

tonic seizures
- mice exhibit bursts of wild running and jumping followed by 5 to 10 seconds of full tonic extension similar to running bouncing seizures (RBS)
- observed seizure fatality rate does not increased with age

References

Brew HM; Gittelman JX; Silverstein RS; Hanks TD; Demas VP; Robinson LC; Robbins CA; McKee-Johnson J; Chiu SY; Messing A; Tempel BL. 2007. Seizures and reduced life span in mice lacking the potassium channel subunit Kv1.2, but hypoexcitability and enlarged Kv1 currents in auditory neurons. J Neurophysiol 98(3):1501-25PubMed: 17634333 MGI: J:131735

Additional - Kcna2^tm1Tem related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Separated PCR:Kcna2alternate1
- Genotyping resources and troubleshooting
Breeding Considerations

While maintaining a live colony, these mice are bred as heteroygotes. Mice homozygous for the mutation die by 17 days of age.
- Additional Breeding and Husbandry Support
Citation
When using the STOCK Kcna2^tm1Tem/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #010744 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
	Heterozygous or wildytpe for Kcna2<tm1Tem>

Related Products and Services

Frozen Mouse Embryo	STOCK Kcna2<tm1Tem>/J	$2595.00
Frozen Mouse Embryo	STOCK Kcna2<tm1Tem>/J	$2595.00
Frozen Mouse Embryo	STOCK Kcna2<tm1Tem>/J	$3373.50
Frozen Mouse Embryo	STOCK Kcna2<tm1Tem>/J	$3373.50

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The Jackson Laboratory's Genotype Promise

The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

Terms Of Use

General Terms and Conditions

Questions about Terms of Use

Additional Use Restrictions Apply

Use of MICE by companies or for-profit entities requires a license prior to shipping.

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Kcna2tm1Tem

Allele Symbol: Kcna2tm1Tem

Disease Terms

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Mammalian Phenotype Terms by Genotype

Genotype: Kcna2tm1Tem/Kcna2tm1TemC3Fe.129S7-Kcna2

nervous system phenotype

behavior/neurological phenotype

respiratory system phenotype

growth/size/body region phenotype

mortality/aging

Genotype: Kcna2tm1Tem/Kcna2tm1Teminvolves: 129S7/SvEvBrd

mortality/aging

nervous system phenotype

behavior/neurological phenotype

growth/size/body region phenotype

Genotype: Kcna2tm1Tem/Kcna2+C3Fe.129S7-Kcna2

behavior/neurological phenotype

nervous system phenotype

Genotype: Kcna2tm1Tem/Kcna2tm1Teminvolves: 129S7/SvEvBrd * C57BL/6

behavior/neurological phenotype

mammalian phenotype

mortality/aging

nervous system phenotype

References

Additional - Kcna2tm1Tem related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Live Mouse

Cryorecovery - Pricing

Related Products and Services

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Additional Use Restrictions Apply

Licensing Information

Kcna2^tm1Tem

Allele Symbol: Kcna2^tm1Tem

Genotype: Kcna2^tm1Tem/Kcna2^tm1Tem
C3Fe.129S7-Kcna2

Genotype: Kcna2^tm1Tem/Kcna2^tm1Tem
involves: 129S7/SvEvBrd

Genotype: Kcna2^tm1Tem/Kcna2⁺
C3Fe.129S7-Kcna2

Genotype: Kcna2^tm1Tem/Kcna2^tm1Tem
involves: 129S7/SvEvBrd * C57BL/6

Additional - Kcna2^tm1Tem related