Overview

Also Known As:Kv1.4^-, Kv1.4-/-, Kv1.4 knock out, Kv1.4KO, Kcna4, Kcna4-/-

Homozygous KV1.4 knockout mice exhibit mild hyperactivity and alterations in the circadian patterns in wheel running behavior. These mice may be useful in studying the role of inactivating A-type (I_A) voltage-gated potassium channels in cardiomyopathy and circadian rhythms.

Donating Investigator

Jeanne Nerbonne, Washington University School of Medicine

Genetic overview

Genetic Background	Generation

Kcna4^tm1Lndn

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Kcna4	potassium voltage-gated channel, shaker-related subfamily, member 4

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Research Applications

Cell Biology Research
Neurobiology Research

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Details

Detailed Description

The Knca4 (potassium channel, voltage gated shaker related subfamily A, member 4) gene encodes an inactivating A-type (transient outward) potassium channel subunit found in the heart and brain and involved in the regulation of the fast repolarizing phase of action potentials.
This KV1.4 knockout allele has a PGK-neo cassette replacing a large portion of the coding region of the Knca4 gene.

Homozygous mice exhibit mild hyperactivity, shorter periods of locomotor activity and alterations in the circadian patterns in wheel running behavior. Neurons of the suprachiasmatic nucleus display increased firing rates and shorter circadian periods.
Spontaneous seizure activity is observed in 10% of homozygous mutants .
These mice may be useful in studying the role of voltage-gated potassium channels in cardiomyopathy and circadian rhythms.

Development

A targeting vector was designed by Dr. Barry London (University of Iowa) to
replace a large section of the coding region of the potassium voltage-gated channel, shaker-related subfamily, member 4 gene (Knca4) on chromosome 2 with a PGK-neo cassette, thereby removing the N-terminal multimerization domain.
The construct was electroporated into 129S4/SvJae-derived J1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts, and chimeric males were bred with C57BL/6 females to establish the colony.
The resulting Kv1.4 knockout mice were bred with C57BL/6J wildtype mice for at least 10 generations. Upon arrival at The Jackson Laboratory, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J oocytes (Stock No. 000664).

Control Suggestions

000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

London B; Wang DW; Hill JA; Bennett PB. 1998. The transient outward current in mice lacking the potassium channel gene Kv1.4. J Physiol 509(Pt 1):171-82PubMed: 9547391 MGI: J:48415

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Genetics

Kcna4^tm1Lndn

Allele Symbol: Kcna4^tm1Lndn

Allele Name	targeted mutation 1, Barry London
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	Kv1.4^-
Gene Symbol and Name	Kcna4, potassium voltage-gated channel, shaker-related subfamily, member 4
Gene Synonym(s)
Strain of Origin	129S4/SvJae
Chromosome	2
Molecular Note	The gene was disrupted by replacement of a large part of the coding region with a PGK-neo cassette resulting in the deletion of the N-terminal multimerization domain. Northern blot analysis of brain RNA from homozygous mutant animals detected a truncated transcript, and Western blot analysis failed to detect the 85 kDa protein in the heart or brain. However, a 65 kDa protein was detected that may possibly be another channel protein that cross-reacts with the anti-Kcna4 antibody.

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Cell Biology Research
- Channel and Transporter Defects
  - potassium
Neurobiology Research
- Channel and Transporter Defects
  - potassium
- Circadian Rhythms

Mammalian Phenotype Terms by Genotype

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

Genotype: Kcna4^tm1Lndn/Kcna4^tm1Lndn
involves: 129S4/SvJae * C57BL/6

behavior/neurological phenotype

seizures
- homozygous null mice were viable, fertile and grossly normal; however, <10% of mutants displayed spontaneous seizure activity

nervous system phenotype

seizures
- homozygous null mice were viable, fertile and grossly normal; however, <10% of mutants displayed spontaneous seizure activity

References

London B; Wang DW; Hill JA; Bennett PB. 1998. The transient outward current in mice lacking the potassium channel gene Kv1.4. J Physiol 509(Pt 1):171-82PubMed: 9547391 MGI: J:48415

Additional - Kcna4^tm1Lndn related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Kcna4-Alternate 1
- Genotyping resources and troubleshooting
Breeding Considerations

While maintaining a live colony, these mice are bred as homozygotes.
- Additional Breeding and Husbandry Support
Citation
When using the Kv1.4^- mouse strain in a publication, please cite the originating article(s) and include MMRRC stock #41480 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

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

See MMRRC for Additional Conditions of Distribution

Questions about Terms of Use

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

Also Known As:Kv1.4-, Kv1.4-/-, Kv1.4 knock out, Kv1.4KO, Kcna4, Kcna4-/-

Donating Investigator

Genetic overview

Research Applications

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Kcna4tm1Lndn

Allele Symbol: Kcna4tm1Lndn

Disease Terms

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Kcna4tm1Lndn/Kcna4tm1Lndninvolves: 129S4/SvJae * C57BL/6

behavior/neurological phenotype

nervous system phenotype

References

Additional - Kcna4tm1Lndn related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

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

The Jackson Laboratory's Genotype Promise

Terms Of Use

Licensing Information

Also Known As:Kv1.4^-, Kv1.4-/-, Kv1.4 knock out, Kv1.4KO, Kcna4, Kcna4-/-

Kcna4^tm1Lndn

Allele Symbol: Kcna4^tm1Lndn

Genotype: Kcna4^tm1Lndn/Kcna4^tm1Lndn
involves: 129S4/SvJae * C57BL/6

Additional - Kcna4^tm1Lndn related