129S/SvEvTac-Hcn1^tm2Kndl/J

Stock number: 028301
Product name: HCN1 ko
Research areas: Cell Biology Research, Developmental Biology Research, Neurobiology Research

Description

The exon encoding the pore region and S6 transmembrane domain of the Hcn1 gene are has been excised in this knockout strain (HCN1 ko). 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 has been excised in this knockout strain (HCN1 ko). Homozygous mice are viable, fertile, and normal in size.

HCN1 ion channels are essential to pacemaker currents in heart and in neurons, where they regulate dendritic excitability. These mice exhibit impaired learning capacity in visible platform swimming water maze task and rotorod test, and abnormal eye blink conditioning response. Purkinje cell electrophysiology is abnormal. This mutant mouse strain may be useful in studies of learning, memory, neurophysiology, and Parkinson's Disease.

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 lacking both the neomycin cassette and floxed exon were injected into C57BL/6 blastocysts. Resulting mice were maintained on a 129S6/SvEvTac background by the donating laboratory.

Allele

Symbol: Hcn1^tm2Kndl
Name: targeted mutation 2, Eric R Kandel
MGI accession ID: MGI:2686951
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Hcn1
Marker name: hyperpolarization-activated, cyclic nucleotide-gated K+ 1
Chromosome: 13
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 both the neomycin gene and the pore-S6 exon were selected. Both mRNA and protein were shown to be absent in the brains of mice homozygous for this allele.