B6.129S-Hcn1^tm2Kndl/J

Stock number: 016566
Research areas: Cell Biology Research, Developmental Biology Research, Neurobiology Research

Description

HCN1 knock-out mice lack the p region and S6 transmembrane (pore-S6) domain of the hyperpolarization-activated, cyclic nucleotide-gated K+ 1 (Hcn1) gene. This mutant mouse strain may be useful in studies of learning, memory, neurophysiology, and Parkinson's Disease.

Detailed description

HCN1 knockout mice lack the p region and S6 transmembrane (pore-S6) domain of the hyperpolarization-activated, cyclic nucleotide-gated K+ 1 (Hcn1) gene. 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

A targeting vector was designed to insert a loxP-flanked neomycin resistance (neo) cassette downstream from the exon encoding the p region and S6 transmembrane (pore-S6) domain of the hyperpolarization-activated, cyclic nucleotide-gated K+ 1 (Hcn1) gene. Another loxP site was inserted upstream of the same exon. The construct was electroporated into 129S/SvEv-derived MM13 embryonic stem (ES) cells which were transiently transfected with a Cre recombinase vector to remove the floxed sequence. Resulting ES cells contained multiple gene rearrangments; intact floxed-exon , intact floxed-neo cassette, or excision of exon and the neo cassette. ES cells, lacking the floxed-exon and the neo cassette, were injected into C57BL/6 blastocysts. The resulting HCN1 knockout offspring were bred to C57BL/6 mice and were subsequently backcrossed to C57BL/6J mice for at least 10 generations. Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation.

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.