The exon encoding the pore region and S6 transmembrane domain of the Hcn1 gene are flanked by loxP sites in this HCN1
Eric R Kandel, Columbia University
The exon encoding the pore region and S6 transmembrane domain of the Hcn1 (hyperpolarization-activated, cyclic nucleotide-gated K+ 1) gene are flanked by loxP sites in this HCN1
Generalized deletion of the HCN1 channel causes profound motor learning and memory deficits in swimming and rotarod tasks. In cerebellar Purkinje cells (a key component of the cerebellar circuit for learning of correctly-timed movements), HCN1 mediates an inward current that stabilizes the integrative properties of Purkinje cells and ensures that their input-ouput function is independent of the previous activity.
Exon 5, encoding both the pore (P) region and the S6 transmembrane domain, was flanked by a pair of loxP sites, and a loxP-flanked thymidine kinase neomycin cassette was inserted immediately downstream via homologous recombination in 129S/SvEv-derived MM13 embryonic stem (ES) cells. ES cells were transiently transfected with a Cre recombinase vector. Clones carrying the floxed exon, but lacking the neomycin cassette were injected into C57BL/6 blastocysts. Resulting mice were backcrossed to C57BL/6J for more than 10 generations by the donating laboratory.
|Allele Name||targeted mutation 1, Eric R Kandel|
|Allele Type||Targeted (Conditional ready (e.g. floxed), No functional change)|
|Gene Symbol and Name||Hcn1, hyperpolarization-activated, cyclic nucleotide-gated K+ 1|
|Site of Expression||When combined with a Cre recombinase-expressing strain, Hcn1 will be excised in cells where promoters driving Cre recombinase are expressed.|
|Strain of Origin||129S/SvEv|
|Molecular Note||A loxP site was inserted upstream of the pore-S6 domain containing exon. At the same time, a floxed neomycin cassette was introduced downstream. Cells in which transient Cre recombinase expression of properly targeted ES cells resulted in excision of neomycin and retention of the pore-S6 exon flanked by loxP sites were selected.|
Floxed homozygotes and heterozygotes are viable and fertile.
When using the HCN1f/f mouse strain in a publication, please cite the originating article(s) and include JAX stock #028299 in your Materials and Methods section.