Overview

Trpc5 (transient receptor potential cation channel, c5) knockout mice exhibit resistance to pilocarpine-induced seizures, minimal seizure-induced neuronal cell death, and reduced long term potentiation.

Donating Investigator

Lutz Birnbaumer, National Institutes of Health

Genetic overview

Genetic Background	Generation

Trpc5^tm1.1Lbi

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Trpc5	transient receptor potential cation channel, subfamily C, member 5

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Research Applications

Cell Biology Research
Neurobiology Research

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Details

Detailed Description

Trpc5 (transient receptor potential cation channel, c5) encodes a multi-pass membrane protein that forms a receptor-activated cation channel. Homozygous knockout mice exhibit resistance to pilocarpine-induced seizures (in the late phase), minimal seizure-induced neuronal cell death in the hippocampus, and reduced long term potentiation. This strain may be useful for studying epileptogenesis and neuronal excitotoxicity.

Development

The targeting vector contains a loxP site inserted upstream of exon 5 and a loxP site inserted downstream of exon 5. In the protein this results in the loss of the transmembrane 5 pore and transmembrane 6 ion channel domain. The construct was electroporated into 129S6/SvEvTac-derived embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. The resulting chimeric animals were interbred and offspring were crossed to B6.Cg-Tg(Sox2-cre)1Amc/J mice to remove exon 5. Offspring were interbred to generate a homozygous colony. Upon arrival, mice were bred to C57BL/6J for at least 1 generation to establish the colony.

Control Suggestions

Approximate Controls

101045 B6129SF2/J

Additional Information

Considerations for Choosing Controls

Selected References

Phelan KD; Shwe UT; Abramowitz J; Wu H; Rhee SW; Howell MD; Gottschall PE; Freichel M; Flockerzi V; Birnbaumer L; Zheng F. 2013. Canonical transient receptor channel 5 (TRPC5) and TRPC1/4 contribute to seizure and excitotoxicity by distinct cellular mechanisms. Mol Pharmacol 83(2):429-38PubMed: 23188715 MGI: J:194590

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Genetics

Trpc5^tm1.1Lbi

Allele Symbol: Trpc5^tm1.1Lbi

Allele Name	targeted mutation 1.1, Lutz Birnbaumer
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)
Gene Symbol and Name	Trpc5, transient receptor potential cation channel, subfamily C, member 5
Gene Synonym(s)
Strain of Origin	129S6/SvEvTac
Chromosome	X
Molecular Note	Exon 5 was floxed via homologous recombination. Cre mediated recombination removed exon 5. Absence of protein expression was confirmed by immunofluorescent staining of the hippocampal region of homozygous mice.

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Cell Biology Research
- Channel and Transporter Defects
Neurobiology Research
- Channel and Transporter Defects
- Epilepsy
  - decreased susceptibility to seizures

Mammalian Phenotype Terms by Genotype

The following phenotype relates to a compound genotype created using this strain

Genotype: Trpc5^tm1.1Lbi/Y
involves: 129S6/SvEvTac * C57BL/6 * CBA

behavior/neurological phenotype

decreased susceptibility to pharmacologically induced seizures
- decrease in the severity of the late phase of pilocarpine induced seizures but the early phase is similar to controls

cellular phenotype

decreased susceptibility to neuronal excitotoxicity
- marked decrease in neuronal cell death in the hippocampus following pilocarpine induced seizures

homeostasis/metabolism phenotype

decreased susceptibility to neuronal excitotoxicity
- marked decrease in neuronal cell death in the hippocampus following pilocarpine induced seizures

mammalian phenotype

behavior/neurological phenotype
- Normal - spatial learning is similar to controls

nervous system phenotype

reduced long term potentiation
- decrease in the potentiation of the fEPSP slope following high-frequency stimulus at Schaffer collateral synapses in the CA1 region

decreased susceptibility to pharmacologically induced seizures
- decrease in the severity of the late phase of pilocarpine induced seizures but the early phase is similar to controls

decreased susceptibility to neuronal excitotoxicity
- marked decrease in neuronal cell death in the hippocampus following pilocarpine induced seizures

Genotype: Trpc5^tm1.1Lbi/Trpc5^tm1.1Lbi
involves: 129S6/SvEvTac * C57BL/6 * CBA

behavior/neurological phenotype

decreased susceptibility to pharmacologically induced seizures
- decrease in the severity of the late phase of pilocarpine induced seizures but the early phase is similar to controls

cellular phenotype

decreased susceptibility to neuronal excitotoxicity
- marked decrease in neuronal cell death in the hippocampus following pilocarpine induced seizures

homeostasis/metabolism phenotype

decreased susceptibility to neuronal excitotoxicity
- marked decrease in neuronal cell death in the hippocampus following pilocarpine induced seizures

mammalian phenotype

behavior/neurological phenotype
- Normal - spatial learning is similar to controls

nervous system phenotype

reduced long term potentiation
- decrease in the potentiation of the fEPSP slope following high-frequency stimulus at Schaffer collateral synapses in the CA1 region

decreased susceptibility to pharmacologically induced seizures
- decrease in the severity of the late phase of pilocarpine induced seizures but the early phase is similar to controls

decreased susceptibility to neuronal excitotoxicity
- marked decrease in neuronal cell death in the hippocampus following pilocarpine induced seizures

References

Phelan KD; Shwe UT; Abramowitz J; Wu H; Rhee SW; Howell MD; Gottschall PE; Freichel M; Flockerzi V; Birnbaumer L; Zheng F. 2013. Canonical transient receptor channel 5 (TRPC5) and TRPC1/4 contribute to seizure and excitotoxicity by distinct cellular mechanisms. Mol Pharmacol 83(2):429-38PubMed: 23188715 MGI: J:194590

Additional - Trpc5^tm1.1Lbi related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Separated PCR:Trpc5
- Genotyping resources and troubleshooting
Breeding Considerations

While maintaining a live colony, these mice carrying this X-linked allele are bred as homozygote female to hemizygous male.
- Additional Breeding and Husbandry Support
Citation
When using the STOCK Trpc5^tm1.1Lbi/Mmjax mouse strain in a publication, please cite the originating article(s) and include MMRRC stock #37349 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

The Jackson Laboratory's Genotype Promise

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.

Terms Of Use

General Terms and Conditions

See MMRRC for Additional Conditions of Distribution

Questions about Terms of Use

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

Donating Investigator

Genetic overview

Research Applications

Detailed Description

Development

Control Suggestions

Approximate Controls

Additional Information

Selected References

Trpc5tm1.1Lbi

Allele Symbol: Trpc5tm1.1Lbi

Disease Terms

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Mammalian Phenotype Terms by Genotype

Genotype: Trpc5tm1.1Lbi/Yinvolves: 129S6/SvEvTac * C57BL/6 * CBA

behavior/neurological phenotype

cellular phenotype

homeostasis/metabolism phenotype

mammalian phenotype

nervous system phenotype

Genotype: Trpc5tm1.1Lbi/Trpc5tm1.1Lbiinvolves: 129S6/SvEvTac * C57BL/6 * CBA

behavior/neurological phenotype

cellular phenotype

homeostasis/metabolism phenotype

mammalian phenotype

nervous system phenotype

References

Additional - Trpc5tm1.1Lbi related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

The Jackson Laboratory's Genotype Promise

Terms Of Use

Licensing Information

Trpc5^tm1.1Lbi

Allele Symbol: Trpc5^tm1.1Lbi

Genotype: Trpc5^tm1.1Lbi/Y
involves: 129S6/SvEvTac * C57BL/6 * CBA

Genotype: Trpc5^tm1.1Lbi/Trpc5^tm1.1Lbi
involves: 129S6/SvEvTac * C57BL/6 * CBA

Additional - Trpc5^tm1.1Lbi related