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 (IA) voltage-gated potassium channels in cardiomyopathy and circadian rhythms.
Jeanne Nerbonne, Washington University School of Medicine
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.
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).
|Allele Name||targeted mutation 1, Barry London|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Kcna4, potassium voltage-gated channel, shaker-related subfamily, member 4|
|Strain of Origin||129S4/SvJae|
|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.|
While maintaining a live colony, these mice are bred as homozygotes.
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.