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.
Eric R Kandel, Columbia University
Genetic Background | Generation |
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Allele Type | Gene Symbol | Gene Name |
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Targeted (Null/Knockout) | Hcn1 | hyperpolarization-activated, cyclic nucleotide-gated K+ 1 |
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.
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 Name | targeted mutation 2, Eric R Kandel |
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Allele Type | Targeted (Null/Knockout) |
Allele Synonym(s) | Hcn1-; HCN1 knockout |
Gene Symbol and Name | Hcn1, hyperpolarization-activated, cyclic nucleotide-gated K+ 1 |
Gene Synonym(s) | |
Strain of Origin | 129S/SvEv |
Chromosome | 13 |
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. |
Mutations Made By | Eric Kandel, Columbia University |
When maintaining a live colony, homozygous mice may be bred together.
When using the B6.129S-Hcn1tm2Kndl/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #016566 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
---|---|---|
Heterozygous or wildtype for Hcn1<tm2Kndl> |
Frozen Mouse Embryo | B6.129S-Hcn1<tm2Kndl>/J | $2595.00 |
Frozen Mouse Embryo | B6.129S-Hcn1<tm2Kndl>/J | $2595.00 |
Frozen Mouse Embryo | B6.129S-Hcn1<tm2Kndl>/J | $3373.50 |
Frozen Mouse Embryo | B6.129S-Hcn1<tm2Kndl>/J | $3373.50 |
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The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.
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