C3HeB.129S7-Kcna1^tm1Tem/J

Stock number: 003532
Product name: Kv1.1-null
Research areas: Cancer Research, Cell Biology Research, Neurobiology Research, Sensorineural Research

Description

These Kcna1 knock-out mice exhibit an epileptic phenotype with approximately 50% of the homozygous mice dying between the third and fifth postnatal week.

Detailed description

Homozygous null mice display an epileptic phenotype (episodic eye blinking, twitching of vibrissae, forelimb paddling, arrested motion, hyperstartle response) beginning during the third postnatal week. Quantitative RNase protection analysis on brain tissue indicates that in heterozygous mice the Kcna1 transcript is reduced to approximately half that observed in wild-type littermates. No transcripts were detected in homozygous mice. Approximately 50% of the homozygous mice die between the third and fifth weeks of life. Mice surviving this period survive for varying periods, depending on genetic background; congenic C3HeB/FeJ mice usually die at 6-8 weeks; hybrid N:NIHS-BC mice have been maintained for over 12 months during which they continue to display spontaneous seizures. A similar phenotype with spontaneous seizures has been observed in mice having 129/Sv, C3HeB/FeJ, C57BL/6 X 129/Sv, and 129/Sv X N:NIHS-BC backgrounds.

Development

A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt the open reading frame. The construct was electroporated into 129S7/SvEvBrd-Hprt+ derived AB1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts. The resulting chimeric animals were crossed to C3HeB/FeJ mice, and then backcrossed to the same for 15 generations.

Allele

Symbol: Kcna1^tm1Tem
Name: targeted mutation 1, Bruce L Tempel
MGI accession ID: MGI:1861959
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Kcna1
Marker name: potassium voltage-gated channel, shaker-related subfamily, member 1
Chromosome: 6
Strain of origin: 129S7/SvEvBrd-Hprt⁺
Molecular note: A neomycin resistance cassette replaced the entire coding region of the gene. RNA from the deleted gene was undetectable by quantitative RNase protection assays of brain tissue from homozygous null mice.