Strain Name:

STOCK Kcna2tm1Tem/J

Stock Number:

010744

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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.

Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Type Mutant Stock; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
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Specieslaboratory mouse
GenerationN2pN1
Generation Definitions
 
Donating InvestigatorDr. Bruce L. Tempel,   Univ of Washington School of Medicine

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 Information

  Control
   Wild-type from the colony
 
  Considerations for Choosing Controls

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

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

Kcna2tm1Tem/Kcna2+

        C3Fe.129S7-Kcna2tm1Tem
  • nervous system phenotype
  • impaired ability to fire action potentials
    • neurons fire fewer action potentials than wild-type mice   (MGI Ref ID J:131735)
    • neurons hypoexcitability does not change depending on the age of mice   (MGI Ref ID J:131735)
  • 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   (MGI Ref ID J:131735)
  • 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   (MGI Ref ID J:131735)

Kcna2tm1Tem/Kcna2tm1Tem

        involves: 129S7/SvEvBrd * C57BL/6
  • mortality/aging
  • complete postnatal lethality
    • mice survive 17+/-2 days   (MGI Ref ID J:131735)
    • observed seizure fatality rate does not increased with age   (MGI Ref ID J:131735)
  • 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)   (MGI Ref ID J:131735)
    • observed seizure fatality rate does not increased with age   (MGI Ref ID J:131735)
  • behavior/neurological phenotype
  • *normal* behavior/neurological phenotype
    • unlike mice homozygous for a null allele of Kcna1, mice do not exhibit hyperexcitability following a cold swim   (MGI Ref ID J:131735)
    • 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)   (MGI Ref ID J:131735)
      • observed seizure fatality rate does not increased with age   (MGI Ref ID J:131735)

Kcna2tm1Tem/Kcna2tm1Tem

        C3Fe.129S7-Kcna2tm1Tem
  • mortality/aging
  • complete postnatal lethality
    • mice survive 17+/-2 days and likely die due to apnea during tonic extension   (MGI Ref ID J:131735)
    • observed seizure fatality rate is 50% and does not increased with age   (MGI Ref ID J:131735)
  • nervous system phenotype
  • abnormal channel response
    • voltage-clamped inwards rectifier potassium current is larger than in wild-type neurons   (MGI Ref ID J:131735)
  • abnormal nervous system electrophysiology
    • neurons exhibit less depolarized sustained membrane potentials and reduced mean resting input resistance compared to wild-type neurons   (MGI Ref ID J:131735)
    • however, treatment with dendrotoxin abolishes the differences in neuron electrophysiology compared to wild-type neurons   (MGI Ref ID J:131735)
    • tityustoxin has no effect on neurons electrophysiology unlike in wild-type mice   (MGI Ref ID J:131735)
    • abnormal action potential
      • neurons exhibit a higher amplitude threshold than wild-type or heterozygous mice   (MGI Ref ID J:131735)
      • almost all neurons have low excitability compared to wild-type neurons   (MGI Ref ID J:131735)
      • however, all other action potentials and properties not dependent on potassium signaling are normal   (MGI Ref ID J:131735)
      • impaired ability to fire action potentials
        • neurons fire one action potentials when stimulated with 200-pA compared to 3 fired by wild-type mice   (MGI Ref ID J:131735)
        • neurons hypoexcitability does not change depending on the age of mice   (MGI Ref ID J:131735)
  • increased susceptibility to pharmacologically induced seizures
    • mice exhibit a shorter latency to seizure following treatment with flurothyl compared to wild-type mice and heterozygotes   (MGI Ref ID J:131735)
    • latency to running bouncing seizures is 40% less than in wild-type mice or heterozygotes   (MGI Ref ID J:131735)
  • 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)   (MGI Ref ID J:131735)
    • observed seizure fatality rate is 50% and does not increased with age   (MGI Ref ID J:131735)
  • growth/size/body phenotype
  • decreased body weight
    • at P14, mice weigh 1 g less than wild-type and heterozygous mice   (MGI Ref ID J:131735)
  • respiratory system phenotype
  • apnea
    • mice likely die due to apnea during tonic extension   (MGI Ref ID J:131735)
  • 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   (MGI Ref ID J:131735)
    • latency to running bouncing seizures is 40% less than in wild-type mice or heterozygotes   (MGI Ref ID J:131735)
  • 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)   (MGI Ref ID J:131735)
    • observed seizure fatality rate is 50% and does not increased with age   (MGI Ref ID J:131735)

Kcna2tm1Tem/Kcna2tm1Tem

        involves: 129S7/SvEvBrd
  • mortality/aging
  • complete postnatal lethality
    • mice exhibit seizures resulting in death by P28   (MGI Ref ID J:130097)
  • nervous system phenotype
  • abnormal brain wave pattern
    • during seizures mice exhibit an ictal electroencephalography (EEG) pattern and abnormal spiking EEG activity   (MGI Ref ID J:130097)
    • 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   (MGI Ref ID J:130097)
  • seizures
    • seizures are rare at P17   (MGI Ref ID J:130097)
    • mice exhibit seizures resulting in death by P28   (MGI Ref ID J:130097)
    • seizures occur during waking or during rapid eye movement sleep   (MGI Ref ID J:130097)
    • during seizures mice exhibit an ictal electroencephalography (EEG) pattern and abnormal spiking EEG activity   (MGI Ref ID J:130097)
  • behavior/neurological phenotype
  • 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   (MGI Ref ID J:130097)
    • mice spend more time in waking during the light phase wild-type and heterozygous mice   (MGI Ref ID J:130097)
    • while the number of episodes of NREM are normal, the duration of NREM is reduced compared to in wild-type mice   (MGI Ref ID J:130097)
    • 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   (MGI Ref ID J:130097)
  • seizures
    • seizures are rare at P17   (MGI Ref ID J:130097)
    • mice exhibit seizures resulting in death by P28   (MGI Ref ID J:130097)
    • seizures occur during waking or during rapid eye movement sleep   (MGI Ref ID J:130097)
    • during seizures mice exhibit an ictal electroencephalography (EEG) pattern and abnormal spiking EEG activity   (MGI Ref ID J:130097)
  • growth/size/body phenotype
  • decreased body size
    • while normal for the first 2 weeks of life, by P16 mice are smaller than wild-type   (MGI Ref ID J:130097)
View Research Applications

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

Cell Biology Research
Channel and Transporter Defects
      potassium

Developmental Biology Research
Postnatal Lethality
      Homozygous

Neurobiology Research
Channel and Transporter Defects
      potassium
Epilepsy

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Kcna2tm1Tem
Allele Name targeted mutation 1, Bruce L Tempel
Allele Type Targeted (Null/Knockout)
Mutation Made ByDr. Bruce Tempel,   Univ of Washington School of Medicine
Strain of Origin129S7/SvEvBrd-Hprt<+>
ES Cell Line NameAB1
ES Cell Line Strain129S7/SvEvBrd-Hprt<+>
Gene Symbol and Name Kcna2, potassium voltage-gated channel, shaker-related subfamily, member 2
Chromosome 3
Gene Common Name(s) Akr6a4; BK2; HBK5; HK4; HUKIV; K+ channel, A current, subtype 1, gene 2; KV1.2; Kca1-2; MK2; Mk-2; NGK1; RBK2; mouse K+ channel gene 2 (brain);
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. [MGI Ref ID J:131735]

Genotyping

Genotyping Information

Genotyping Protocols

Kcna2tm1Temalternate1,

SEPARATED MELT



Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

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):1501-25. [PubMed: 17634333]  [MGI Ref ID J:131735]

Additional References

Kcna2tm1Tem related

Douglas CL; Vyazovskiy V; Southard T; Chiu SY; Messing A; Tononi G; Cirelli C. 2007. Sleep in Kcna2 knockout mice. BMC Biol 5:42. [PubMed: 17925011]  [MGI Ref ID J:130097]

Fulton S; Thibault D; Mendez JA; Lahaie N; Tirotta E; Borrelli E; Bouvier M; Tempel BL; Trudeau LE. 2011. Contribution of Kv1.2 Voltage-gated Potassium Channel to D2 Autoreceptor Regulation of Axonal Dopamine Overflow. J Biol Chem 286(11):9360-72. [PubMed: 21233214]  [MGI Ref ID J:170639]

Health & husbandry

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Health & Colony Maintenance Information

Animal Health Reports

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

Colony Maintenance

Breeding & HusbandryWhile maintaining a live colony, these mice are bred as heteroygotes. Mice homozygous for the mutation die by 17 days of age.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


Pricing for USA, Canada and Mexico shipping destinations View International Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $2525.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.

    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $3283.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.

    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Control Information

  Control
   Wild-type from the colony
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

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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.
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