B6.129S-Hcn1^tm1Kndl/J

Stock number: 028299
Product name: HCN1^f/f
Research areas: Neurobiology Research, Research Tools

Description

The exon encoding the pore region and S6 transmembrane domain of the Hcn1 gene are flanked by loxP sites in this HCN1 strain. Cre-mediated excision of the floxed region creates a knockout allele. This mutant mouse strain may be useful in studies of learning, memory, neurophysiology, and Parkinson's Disease.

Detailed description

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 strain. Cre-mediated excision of the floxed region creates a knockout allele. Homozygous floxed mice are born at predicted Mendelian ratios and do not differ from their wildtype littermates in overall health and longevity.

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.

Development

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

Symbol: Hcn1^tm1Kndl
Name: targeted mutation 1, Eric R Kandel
MGI accession ID: MGI:2686950
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); No functional change
Marker symbol: Hcn1
Marker name: hyperpolarization-activated, cyclic nucleotide-gated K+ 1
Chromosome: 13
Strain of origin: 129S/SvEv
Site of expression: When combined with a Cre recombinase-expressing strain, Hcn1 will be excised in cells where promoters driving Cre recombinase are expressed.
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.