Overview

Also Known As:SK2T

The SK2^T mutant allele results in approximately ten-fold overexpression of the Kcnn2 (potassium intermediate/small conductance calcium-activated channel, subfamily N, member 2; also called SK2) gene product prior to administration of tetracycline (or its analog doxycycline (dox)). These SK2-tTA mice may be useful in studying the role of small-conductance calcium-activated potassium (SK) channels in after-hyperpolarization and action potentials in neurobiology, hippocampal synaptic plasticity, learning and memory, and fear conditioning.

Donating Investigator

John P Adelman, Vollum Inst. Oregon Health & Sci. Univ.

Genetic overview

Genetic Background	Generation

Kcnn2^tm2Jpad

Allele Type	Gene Symbol	Gene Name
Targeted (Inserted expressed sequence)	Kcnn2	potassium intermediate/small conductance calcium-activated channel, subfamily N, member 2

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Research Applications

Research Tools
Neurobiology Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

The SK2^T mutant allele has a tetracycline-based genetic switch inserted into the 5' UTR of the targeted gene, just upstream of the translation initiation site. This genetic switch harbors both the tetracycline-controlled transactivator protein (tTA) as well as the tetracycline operator (tetO; also called tetracycline-responsive element (TRE) or tet-operator). The donating investigator reports that long term administration of tetracycline (or its analog doxycycline (dox)) does not block transcription of the downstream Kcnn2 locus. The donating investigator also reports that homozygous mice are viable but do not thrive without dox treatment. SK2-tTA heterozygotes (SK2^T) exhibit approximately ten-fold overexpression of SK2 protein before dox treatment. In the absence of dox, homozygous mice exhibit enhanced SK channel-mediated restriction of glutamatergic activity in CA1 neurons, attenuated hippocampal synaptic plasticity, impaired spatial learning and memory in the Morris water maze, and impaired contextual and cued fear conditioning.

Development

A targeting construct was designed with (from 5' to 3') an adenovirus tripartite leader sequence, a binary tetracycline controlled transactivator (tTA) protein, an SV40 polyA signal, a loxP-flanked selection cassette (neomycin resistance and yeast URA3 gene), an hGH polyA signal, and 5 copies of the tetracycline operator (tetO; also called tetracycline-responsive element (TRE) or tet-operator) sequence fused to the cytomegalovirus minimal promoter. This construct was designed to insert 40 bp upstream of the most 5' methionine codon of the targeted gene. The construct was electroporated into 129/SvJae-derived embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts. To remove the floxed selection cassette, chimeric mice were bred to CMV-Cre mice (reported to be C57BL/6J genetic background; see Stock No. 006054). The donating investigator reports that heterozygous (SK2-tTA or SK2^T) mice were subsequently backcrossed for approximately 20 generations to C57BL/6J mice prior to arrival at The Jackson Laboratory. Upon arrival, mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the colony.

Expression Data

Expressed Gene	tTA, tetracycline-controlled transactivator, E. coli
Site of Expression	In the absence of dox, homozygous mice exhibit enhanced SK channel-mediated restriction of glutamatergic activity in CA1 neurons, attenuated hippocampal synaptic plasticity, impaired spatial learning and memory in the Morris water maze, and impaired contextual and cued fear conditioning.

Control Suggestions

Wild-type from the colony
000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Hammond RS; Bond CT; Strassmaier T; Ngo-Anh TJ; Adelman JP; Maylie J; Stackman RW. 2006. Small-conductance Ca2+-activated K+ channel type 2 (SK2) modulates hippocampal learning, memory, and synaptic plasticity. J Neurosci 26(6):1844-53PubMed: 16467533 MGI: J:105645

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Genetics

Kcnn2^tm2Jpad

Allele Symbol: Kcnn2^tm2Jpad

Allele Name	targeted mutation 2, John P Adelman
Allele Type	Targeted (Inserted expressed sequence)
Allele Synonym(s)	mSK2 tTAdeltaneo; SK2T
Gene Symbol and Name	Kcnn2, potassium intermediate/small conductance calcium-activated channel, subfamily N, member 2
Gene Synonym(s)
Promoter	tetO, tet operator,
Expressed Gene	tTA, tetracycline-controlled transactivator, E. coli
Site of Expression	In the absence of dox, homozygous mice exhibit enhanced SK channel-mediated restriction of glutamatergic activity in CA1 neurons, attenuated hippocampal synaptic plasticity, impaired spatial learning and memory in the Morris water maze, and impaired contextual and cued fear conditioning.
Strain of Origin	129S4/SvJae
Chromosome	18
Molecular Note	A genetic switch based on the tetracycline transactivator/tetracycline operator (tTA/tetO) system was inserted into the 5' untranslated region (5' UTR) of the targeted gene 40 nucleotides upstream of the initiator ATG. The switch, after in vivo excision of a selection cassette, comprises a tripartite adenovirus leader sequence (to enhance translation initiation efficiency) followed by the coding sequence for the tTA protein with SV40 and human growth hormone polyadenylation signals separated by a single loxP site; and five copies of the tetracycline operator (tetO), also called the tetracycline responsive element (TRE), joined to the cytomegalovirus (CMV) minimal promoter. In the absence of doxycycline (Dox), heterozygous mutant mice express 4.5-fold the wild-type level of Kcnn2 mRNA and 10-fold the wild-type level of Kcnn2 subunit protein, respectively assessed by quantitative and real-time PCR of whole-brain RNA and by immunoblot analysis of membrane proteins from whole brains. Administration of Dox reduces, but does not eliminate, expression from the mutant allele.
Mutations Made By	John Adelman, Vollum Inst. Oregon Health & Sci. Univ.

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Research Tools
- Genetics Research
  - Mutagenesis and Transgenesis
  - Mutagenesis and Transgenesis: Tetop Tet System
- Cardiovascular Research
  - Tetop Tet System
- Neurobiology Research
  - Tetop Tet System
- Reproductive Biology Research
  - Tetop Tet System
- Tet Expression Systems
  - tTA/rtTA Expressing Strains
  - tTA/rtTA Responsive Strains
Neurobiology Research
- Behavioral and Learning Defects
- Tet Expression System
  - tTA/rtTA Responsive Strains
  - tTA/rtTA Expressing Strains

Mammalian Phenotype Terms by Genotype

The following phenotype relates to a compound genotype created using this strain

Genotype: Kcnn2^tm2Jpad/Kcnn2⁺
B6.129S4-Kcnn2

behavior/neurological phenotype

abnormal contextual conditioning behavior

abnormal cued conditioning behavior

abnormal spatial learning
- longer cumulative distance to target in Morris water maze tests

nervous system phenotype

abnormal excitatory postsynaptic potential
- EPSP in CA1 neurons increases136% as opposed to 59% for controls after apamin treatment
- no effect on paired-pulse facilitation

reduced long term potentiation
- LTP induced by three 50Hz tetani was significantly reduced

abnormal CNS synaptic transmission
- four fold increase in the amplitude of apamin sensitive currents in CA1 neurons

Genotype: Kcnn2^tm2Jpad/Kcnn2^tm2Jpad
B6.129S4-Kcnn2

mortality/aging

prenatal lethality, complete penetrance
- not viable unless treated prenatally with doxycycline

References

Hammond RS; Bond CT; Strassmaier T; Ngo-Anh TJ; Adelman JP; Maylie J; Stackman RW. 2006. Small-conductance Ca2+-activated K+ channel type 2 (SK2) modulates hippocampal learning, memory, and synaptic plasticity. J Neurosci 26(6):1844-53PubMed: 16467533 MGI: J:105645

Additional - Kcnn2^tm2Jpad related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Kcnn2 STD PCR
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, heterozygous mice may be bred together, to wildtype siblings, or to C57BL/6J inbred mice (Stock No. 000664). The donating investigator also reports that homozygous mice are viable but do not thrive without doxycycline treatment.
- Additional Breeding and Husbandry Support
Citation
When using the SK2T mouse strain in a publication, please cite the originating article(s) and include JAX stock #009602 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

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Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
> >	Heterozygous or Wild-Type for Kcnn2<tm2Jpad>

Related Products and Services

Frozen Mouse Embryo	B6.129S4(Cg)-Kcnn2<tm2Jpad>/J Frozen Embryo	$2595.00
Frozen Mouse Embryo	B6.129S4(Cg)-Kcnn2<tm2Jpad>/J Frozen Embryo	$2595.00
Frozen Mouse Embryo	B6.129S4(Cg)-Kcnn2<tm2Jpad>/J Frozen Embryo	$3373.50
Frozen Mouse Embryo	B6.129S4(Cg)-Kcnn2<tm2Jpad>/J Frozen Embryo	$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.

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Additional Use Restrictions Apply

Use of MICE by companies or for-profit entities requires a no-fee JAX Leap License prior to shipping.

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

Also Known As:SK2T

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Expression Data

Control Suggestions

Additional Information

Selected References

Kcnn2tm2Jpad

Allele Symbol: Kcnn2tm2Jpad

Disease Terms

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Kcnn2tm2Jpad/Kcnn2+B6.129S4-Kcnn2

behavior/neurological phenotype

nervous system phenotype

Genotype: Kcnn2tm2Jpad/Kcnn2tm2JpadB6.129S4-Kcnn2

mortality/aging

References

Additional - Kcnn2tm2Jpad 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

Kcnn2^tm2Jpad

Allele Symbol: Kcnn2^tm2Jpad

Genotype: Kcnn2^tm2Jpad/Kcnn2⁺
B6.129S4-Kcnn2

Genotype: Kcnn2^tm2Jpad/Kcnn2^tm2Jpad
B6.129S4-Kcnn2

Additional - Kcnn2^tm2Jpad related