B6;129-Kcnq2^tm1.1Avtz/J

Stock number: 036075
Product name: Kcnq2^fl
Research areas: Mouse/Human Gene Homologs, Neurobiology Research, Research Tools

Description

Kcnq2^fl mutant mice possess loxP sites flanking exons 2-5 of the epilepsy-associated Kcnq2 (potassium voltage-gated channel, subfamily Q, member 2) gene and may be useful in generating conditional mutations to study the regulation of neuronal excitability.

Detailed description

Kcnq2 (potassium voltage-gated channel, subfamily Q, member 2) encodes an integral membrane protein that associates with Kncq3 to form the M current, a potassium channel involved in the regulation of pyramidal neuron excitability and spike behavior. Mutations in Kcnq2 are associated with some types of epilepsy. These conditional Kcng2^fl mice possess loxP sites flanking exons 2-5 of the Kcnq2 gene. Mice homozygous for the mutation are viable and fertile. When bred to mice that express tissue-specific Cre recombinase, resulting offspring will have the exons 2-5 deleted in cre-expressing tissues. This strain may be useful for studies involving the regulation of neuronal excitability.

For example, when bred to mice with Cre recombinase expression in the cerebral cortex (Emx1^tm1(cre)Krj, Stock No. 005628), resulting knockout offspring exhibit a reduction of the M current by 85%, increased excitability in CA1 pyramidal neurons, abnormal electrocorticogram activity and premature death.

Development

The targeting construct was designed to insert a loxP site downstream of exon 1 and an FRT-flanked neomycin cassette followed by a second loxP site downstream of exon 5 of the Kcnq2 gene on chromosome 2. Exons 2-5 include sequence encoding the pore region of the Kcnq2 potassium channel. The construct was electroporated into (C57BL/6Jx129/Sv)F1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. Chimeric males were crossed to B6.129S4-Gt(ROSA)26Sor^tm1(FLP1)Dym females (ROSA26-Flpe) to delete the neo cassette. The resulting progeny were crossed to remove the FLP-expressing transgene. The colony was crossed to C57BL/6J for at least 5 generations by the donating laboratory (see SNP note below). Upon arrival, mice were bred to C57BL/6J (000664) for at least one generation to establish the colony.

In 2020, a 48 SNP (single nucleotide polymorphism) panel analysis, with 43 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the males sent to The Jackson Laboratory Repository. Markers on Chromosomes 1, 7, 12, 15, and 16 were segregating with 129. Also, three of the 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating, including the rd8 recessive mutation associated with retinal degeneration on Chromosome 1 within the Crb1 locus. These data suggest the mice sent to The Jackson Laboratory Repository were on a mixed genetic background.

Allele

Symbol: Kcnq2^tm1.1Avtz
Name: targeted mutation 1.1, Anastasios V Tzingounis
MGI accession ID: MGI:5607735
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); No functional change
Synonyms: Kcnq2^fl
Marker symbol: Kcnq2
Marker name: potassium voltage-gated channel, subfamily Q, member 2
Marker synonyms: BFNC; DEE7; EBN; EBN1; ENB1; HNSPC; KCNA11; KQT2; KV7.2; Nmf134
Chromosome: 2
Strain of origin: (C57BL/6J x 129/Sv)F1
Molecular note: Exons 2-5 were floxed and an FRT flanked neomycin cassette was inserted via homologous recombination. Flp mediated recombination removed the neomycin cassette.