Slack (Slo2.2) floxed mice possess loxP sites flanking exon 11 of the Kcnt1 gene, making this strain useful for studying the regulation of neuronal excitability and intellectual disabilities caused by mutations in Slack channels.
Christopher J. Lingle, Washington University School of Medicine
Slack (Slo2.2) floxed mice possess loxP sites flanking exon 11 of the potassium channel, subfamily T, member 1 (Kcnt1) gene. KCNT1 encodes a subunit of a sodium activated potassium channel expressed in neurons throughout the brain. SLACK is involved in the regulation of neuronal excitability and the rate of adaptation in response to repeated stimulation. Mutations in this gene have been associated with Early Infantile Epileptic Encephalopathy and Fragile X syndrome. Slack floxed mice that are homozygous for this allele are viable and fertile. When bred to mice that express tissue-specific Cre recombinase, resulting offspring will have exon 11 of the Kcnt1 gene deleted in cre-expressing tissues.
A targeting vector was designed by Dr. Xiao-Ming Xia (laboratory of Dr. Christopher Lingle, Washington University School of Medicine) to insert a loxP site upstream of exon 11 of the potassium channel, subfamily T, member 1 (Kcnt1) gene. The construct also inserted a second loxP site, followed by a frt-flanked neomycin resistance (neo) cassette which included a third loxP site, downstream of exon 11. The construct was electroporated into B6/129X1Sv-derived embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and resulting chimeric mice were bred with B6.129S4-Gt(ROSA)26Sortm1(FLP1)Dym/RainJ mice (Stock No. 009086) to delete the neo cassette. Resulting progeny were crossed to remove the Flp-expressing transgene, and Slack floxed offspring were backcrossed to C57BL/6J mice for at least 15 generations. Upon arrival, 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 1.1, Christopher J Lingle|
|Allele Type||Targeted (Conditional ready (e.g. floxed), No functional change)|
|Allele Synonym(s)||Slack floxed|
|Gene Symbol and Name||Kcnt1, potassium channel, subfamily T, member 1|
|Strain of Origin||C57BL/6 x 129X1/SvJ|
|Molecular Note||A targeting vector was designed to insert a loxP site upstream of exon 11 and a second loxP site, followed by an FRT-flanked neomycin resistance (neo) cassette which includes a third loxP site, downstream of exon 11. Flp-mediated recombination removed the FRT-flanked neo cassette leaving exon 11 floxed.|
When maintaining a live colony, homozygous mice may be bred together.
When using the Slack floxed mouse strain in a publication, please cite the originating article(s) and include JAX stock #028418 in your Materials and Methods section.