Overview

Also Known As:TRPM8 KO

These transient receptor potential cation channel, subfamily M, member 8 (Trpm8) knock-out mutant mice may be useful for neurological studies including thermosensation over a wide range of cold temperatures, detection of cold thermal stimuli by primary afferent sensory neurons, nociceptive processing, and pain response behavior.

Donating Investigator

Dr. David Julius, Univ of California at San Francisco

Genetic overview

Genetic Background	Generation
	N5+N2F11 (2020-04-13 00:00:00)

Trpm8^tm1Jul

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Trpm8	transient receptor potential cation channel, subfamily M, member 8

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Research Applications

Sensorineural Research
Research Tools

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Base Price

Starting at:

$255.00 Domestic price for female 4-week

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Details

Detailed Description

Mice homozygous for this TRPM8 targeted mutation are viable and fertile, with no differences in core body temperature compared to wildtype. Functional TRPM8 transcripts are absent in trigeminal ganglia from homozygous mutants however,a truncated, non-functional transcript is generated. Immunostaining of trigeminal ganglia, corneal afferents, and spinal cord dorsal horn reveals loss of TRPM8 expression in homozygous mutants. TRPM8-deficient mice exhibit behavioral deficits in their ability to discriminate between cold and warm surfaces, or to respond to evaporative cooling. Homozygous mice are not completely cold insensitive as they avoid contact with surfaces below 10 C (albeit with reduced efficiency). Cultured sensory neurons and intact sensory nerve fibers from TRPM8-deficient mice exhibit profoundly diminished responses to cold. These TRMP8 (transient receptor potential cation channel, subfamily M, member 8 (also called TRP melastatin 8 or cold and menthol receptor 1 (CMR1))) mutant mice may be useful for neurological studies including thermosensation over a wide range of cold temperatures, detection of cold thermal stimuli by primary afferent sensory neurons, nociceptive processing, and pain response behavior.

Development

A targeting vector was designed to replace 569 base pairs of genomic sequence within exons 13 and 14 (encoding amino acids 594-661 within the presumptive cytoplasmic amino-terminal domain) of the targeted gene with an ACN cassette. The ACN cassette, containing the neomycin resistance gene and cre recombinase gene under the control of angiotensin-converting enzyme promoter, is flanked by loxP sites. Cre-mediated recombination during spermatogenesis removed the cassette, leaving one loxP site and introducing a stop codon before and a frameshift after the deleted segment. The construct was electroporated into 129P2/OlaHsd-derived E14Tg2A.4 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts, and chimeric males were bred to C57BL/6 females. The Donating investigator reported that heterozygous males were then backcrossed to C57BL/6 females (see SNP note below) for 4 generations. Upon arrival at The Jackson Laboratory, mice were backcrossed to C57BL/6J for at least one generation to establish the colony. The Y chromosome may not have been fixed to the C57BL/6N genetic background.

A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. While the 27 markers throughout the genome suggested a C57BL/6 genetic background, all 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a C57BL/6N genetic background.

Control Suggestions

Wild-type from the colony

Approximate Controls

000664 C57BL/6J, (See SNP note
)
005304 C57BL/6NJ, (See SNP note
)

Additional Information

Considerations for Choosing Controls

Selected References

Bautista DM; Siemens J; Glazer JM; Tsuruda PR; Basbaum AI; Stucky CL; Jordt SE; Julius D. 2007. The menthol receptor TRPM8 is the principal detector of environmental cold. Nature 448(7150):204-8PubMed: 17538622 MGI: J:122978

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Genetics

Trpm8^tm1Jul

Allele Symbol: Trpm8^tm1Jul

Allele Name	targeted mutation 1, David Julius
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	trpm8^-(DJ); Trpm8^-
Gene Symbol and Name	Trpm8, transient receptor potential cation channel, subfamily M, member 8
Gene Synonym(s)
Strain of Origin	129P2/OlaHsd
Chromosome	1
Molecular Note	The self excising ACN cassette was inserted to replace exons 13 and 14. Amino acids 594-661, located in the presumptive cytoplasmic amino-terminal domain, were deleted from the locus, introducing a premature stop codon before and a frame shift after the deleted region. RT-PCR confirmed absence of transcript from mutant trigeminal ganglia.
Mutations Made By	Dr. David Julius, Univ of California at San Francisco

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Sensorineural Research
- Nociception
Research Tools
- Sensorineural Research

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Trpm8^tm1Jul/Trpm8^tm1Jul
involves: 129P2/OlaHsd * C57BL/6

behavior/neurological phenotype

increased thermal nociceptive threshold
- mice respond less to cold stimuli

abnormal thermosensation
- mice have no preference for a room temperature surface over a cold surface as wild-type mice do

integument phenotype

increased thermal nociceptive threshold
- mice respond less to cold stimuli

References

Bautista DM; Siemens J; Glazer JM; Tsuruda PR; Basbaum AI; Stucky CL; Jordt SE; Julius D. 2007. The menthol receptor TRPM8 is the principal detector of environmental cold. Nature 448(7150):204-8PubMed: 17538622 MGI: J:122978

Additional - Trpm8^tm1Jul related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Trpm8
- Genotyping resources and troubleshooting
Dietary Information
- LabDiet® 5K52 formulation (6% fat)
Breeding Considerations

When maintaining a live colony, homozygous mice may be bred.
- Additional Breeding and Husbandry Support
Mating System
- Homozygote x Homozygote
Citation
When using the TRPM8 KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #008198 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

AX10 (Standard)

Pricing & Availability

Available

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
	Heterozygous or Wild-Type for Trpm8<tm1Jul>

Related Products and Services

Frozen Mouse Embryo	B6.129P2-Trpm8<tm1Jul>/J Frozen Embryo	$2595.00
Frozen Mouse Embryo	B6.129P2-Trpm8<tm1Jul>/J Frozen Embryo	$2595.00
Frozen Mouse Embryo	B6.129P2-Trpm8<tm1Jul>/J Frozen Embryo	$3373.50
Frozen Mouse Embryo	B6.129P2-Trpm8<tm1Jul>/J Frozen Embryo	$3373.50

Payment Terms and Conditions

Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

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

Questions about Terms of Use

Additional Use Restrictions Apply

Use of MICE by companies or for-profit entities requires a license prior to shipping.

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

Also Known As:TRPM8 KO

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Approximate Controls

Additional Information

Selected References

Trpm8tm1Jul

Allele Symbol: Trpm8tm1Jul

Disease Terms

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Trpm8tm1Jul/Trpm8tm1Julinvolves: 129P2/OlaHsd * C57BL/6

behavior/neurological phenotype

integument phenotype

References

Additional - Trpm8tm1Jul related

Genotyping Protocols

Dietary Information

Breeding Considerations

Mating System

Citation

Animal Health Reports

Live Mouse

Cryorecovery - Pricing

Related Products and Services

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Additional Use Restrictions Apply

Licensing Information

Trpm8^tm1Jul

Allele Symbol: Trpm8^tm1Jul

Genotype: Trpm8^tm1Jul/Trpm8^tm1Jul
involves: 129P2/OlaHsd * C57BL/6

Additional - Trpm8^tm1Jul related