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| The SK2T 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. | |||||||||||||||||||
- Description
- Disease & phenotype
- Genes & alleles
- Genotyping
- Health & care
- References
- Pricing & purchasing
- Terms of use
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
Former Names B6.129(Cg)-Kcnn2tm2Jpad/J (Changed: 13-MAY-09 ) Type Congenic; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Species laboratory mouse Donating Investigator John P Adelman, Vollum Inst. Oregon Health & Sci. Univ. Description
The SK2T 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 (SK2T) 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 SK2T) 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.
Control Information
| Control | ||
|---|---|---|
| Wild-type from the colony | ||
| 000664 C57BL/6J | ||
| Considerations for Choosing Controls | ||
Related Strains
Strains carrying other alleles of Kcnn2
009592 B6.129(Cg)-Kcnn2tm1.1Jpad/J View Strains carrying other alleles of Kcnn2 (1 strain)
Additional Web Information
Tet Expression Systems
Phenotype
Phenotype Information
assigned by genotype
Kcnn2tm2Jpad/Kcnn2+
B6.129S4-Kcnn2tm2Jpad
- nervous system phenotype
- abnormal CNS synaptic transmission
- four fold increase in the amplitude of apamin sensitive currents in CA1 neurons (MGI Ref ID J:105645)
- abnormal excitatory postsynaptic potential
- reduced long term potentiation
- LTP induced by three 50Hz tetani was significantly reduced (MGI Ref ID J:105645)
- behavior/neurological phenotype
- abnormal contextual conditioning behavior (MGI Ref ID J:105645)
- abnormal cued conditioning behavior (MGI Ref ID J:105645)
- abnormal spatial learning
- longer cumulative distance to target in Morris water maze tests (MGI Ref ID J:105645)
Kcnn2tm2Jpad/Kcnn2tm2Jpad
B6.129S4-Kcnn2tm2Jpad
- mortality/aging
- complete prenatal lethality
- not viable unless treated prenatally with doxycycline (MGI Ref ID J:105645)
This mouse can be used to support research in many areas including:
Neurobiology Research
Behavioral and Learning Defects
Tet Expression System
tTA/rtTA Expressing Strains
tTA/rtTA Responsive Strains
Research Tools
Cardiovascular Research
Tetop Tet System
Genetics Research
Mutagenesis and Transgenesis
Mutagenesis and Transgenesis: 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
Genes & Alleles
Gene & Allele Information provided by MGI
| Allele Symbol | Kcnn2tm2Jpad | ||
|---|---|---|---|
| Allele Name | targeted mutation 2, John P Adelman | ||
| Allele Type | Targeted (knock-in) | ||
| Common Name(s) | SK2T; mSK2 tTAdeltaneo; | ||
| Mutation Made By | John Adelman, Vollum Inst. Oregon Health & Sci. Univ. | ||
| Strain of Origin | 129S4/SvJae | ||
| 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. | ||
| Expressed Gene | tetO, tet operator, | ||
| Expressed Gene | tTA, tetracycline-controlled transactivator, E. coli | ||
| The tetracycline-resistance gene (TetR), arose from chemically mutated Escherichia coli genome which was screened for tetracycline dependence (Gossen and Bujard, 1992). TetR was fused at the C-terminus with the viral co-activator, virion protein 16 of the herpes simplex virus (VP-16). The tetracycline-inhibitable transcription factor is a component of a bigenic system that allows doxycycline (a tetracycline analog) regulatable expression of genes that are under the direction of the tetracycline responsive promoter (TetOp)promoter. | |||
| 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 thewild-type level of SK2 mRNA and 10-fold the wild-type level of SK2 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. [MGI Ref ID J:105645] [MGI Ref ID J:95064] | ||
| Gene Symbol and Name | Kcnn2, potassium intermediate/small conductance calcium-activated channel, subfamily N, member 2 | ||
| Chromosome | 18 | ||
| Gene Common Name(s) | KCa2.2; SK2; SKCA2; fri; frissonant; hSK2; small conductance calcium-activated potassium channel 2; | ||
Genotyping
Genotyping Information
Genotyping Protocols
Generic Cre Melt Curve Analysis, Melt Curve Analysis
Helpful Links
Genotyping resources and troubleshooting
References
References provided by MGI
Selected Reference(s)
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):1844-53. [PubMed: 16467533] [MGI Ref ID J:105645]
Additional References
Kcnn2tm2Jpad relatedAllen D; Bond CT; Lujan R; Ballesteros-Merino C; Lin MT; Wang K; Klett N; Watanabe M; Shigemoto R; Stackman RW Jr; Maylie J; Adelman JP. 2011. The SK2-long isoform directs synaptic localization and function of SK2-containing channels. Nat Neurosci 14(6):744-9. [PubMed: 21602822] [MGI Ref ID J:174023]
Bond CT; Sprengel R; Bissonnette JM; Kaufmann WA; Pribnow D; Neelands T; Storck T; Baetscher M; Jerecic J; Maylie J; Knaus HG; Seeburg PH; Adelman JP. 2000. Respiration and parturition affected by conditional overexpression of the Ca2+-activated K+ channel subunit, SK3. Science 289(5486):1942-6. [PubMed: 10988076] [MGI Ref ID J:95064]
Maison SF; Parker LL; Young L; Adelman JP; Zuo J; Liberman MC. 2007. Overexpression of SK2 channels enhances efferent suppression of cochlear responses without enhancing noise resistance. J Neurophysiol 97(4):2930-6. [PubMed: 17267753] [MGI Ref ID J:149054]
Thorneloe KS; Knorn AM; Doetsch PE; Lashinger ES; Liu AX; Bond CT; Adelman JP; Nelson MT. 2008. Small-conductance, Ca2+-activated K+ channel 2 is the key functional component of SK channels in mouse urinary bladder. Am J Physiol Regul Integr Comp Physiol 294(5):R1737-43. [PubMed: 18353877] [MGI Ref ID J:134672]
Wimmer RD; Astori S; Bond CT; Rovo Z; Chatton JY; Adelman JP; Franken P; Luthi A. 2012. Sustaining sleep spindles through enhanced SK2-channel activity consolidates sleep and elevates arousal threshold. J Neurosci 32(40):13917-28. [PubMed: 23035101] [MGI Ref ID J:190926]
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 & Husbandry 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.
Pricing and Purchasing
Pricing, Supply Level & Notes, Controls
| Pricing for USA, Canada and Mexico shipping destinations |
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Cryopreserved
Cryopreserved Mice - Ready for Recovery
Animals Provided
Price (US dollars $) Cryorecovery* $1980.00 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 11 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 |
|
Cryopreserved
Cryopreserved Mice - Ready for Recovery
Animals Provided
Price (US dollars $) Cryorecovery* $2574.00 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 11 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).
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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 | ||
| 000664 C57BL/6J | ||
| 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.Ordering Information
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