This targeted mutation of the potassium voltage-gated channel, shaker-related subfamily, member 2 (Kcna2) gene exhibits spontaneous seizures may be useful in studies of voltage dependent potassium channels and epilepsy.
Dr. Bruce L. Tempel, Univ of Washington School of Medicine
Homozygous mice appear normal at birth, however, by day 15 mice are smaller and exhibit explosive running and bouncing seizures sometimes followed by tonic extension accompanied by a shortness of breath (apnea). These seizures occur at a rate of less than one per day and have a 50% fatality rate. Mean lifespan is approximately 17 days on both the mixed C57BL/6-129S7 background and the C3H background. In homozygous mice, auditory neurons of the medial nucleus of the trapezoid body (MNTB) exhibit a decrease in action potential firing (hypoexcitable) and higher threshold current amplitude than wild-type mice. MNTB neurons in heterozygous mice exhibit an intermediate phenotype. The counter-intuitive decrease in activity with the deletion of Kv1.2 subunits occurs because replacement subunits (most likely Kv1.1) are lower-threshold than Kv1.2. This mutant mouse strain may be useful in studies of voltage dependent potassium channels and epilepsy.
In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.
A targeting vector containing the neomycin resistance gene was used to replace the open reading frame of the targeted gene. The construct was electroporated into 129S7/SvEvTac derived AB1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. The resulting chimeric animals were crossed to C3HeB/FeJ and backcrossed for greater than 30 generations. In 2008, as a result of breeding difficulties, the strain was backcrossed to CBA/CaJ for 2 generations. Upon arrival, mice were bred to C3HeB/FeJ for at least 1 generation to establish the colony.
|Allele Name||targeted mutation 1, Bruce L Tempel|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Kcna2, potassium voltage-gated channel, shaker-related subfamily, member 2|
|Gene Synonym(s)||Akr6a4; BK2; EIEE32; HBK5; HK4; HUKIV; K+ channel, A current, subtype 1, gene 2; KV1.2; Kca1-2; Kca1-2; Kv1.2; MK2; Mk-2; Mk-2; NGK1; RBK2; mouse K+ channel gene 2 (brain)|
|Strain of Origin||129S7/SvEvBrd-Hprt<+>|
|Molecular Note||A neomycin resistance cassette replaced the entire open reading frame. mRNAQ cannot be found by quantitative PCR and protein product cannot be identified by Western blot in extracts from homozygous mutant mice.|
|Mutations Made By|| |
Dr. Bruce Tempel, Univ of Washington School of Medicine
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