Strain Name:

B6;129P-Trpa1tm1Kykw/J

Stock Number:

006401

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Availability:

Repository- Live

Use Restrictions Apply, see Terms of Use
The targeting vector contains an endoplasmic reticulum retention signal and an IRES-PLAP reporter gene, allowing extracellular antibody staining/chromogenic development tracking of cells normally expressing the endogenous gene. Homozygous mice display behavioral deficits in response to mustard oil, cold, and punctate mechanical stimuli. These mutants may be useful in neurobiological studies involving dorsal root ganglion neurons and cells of the inner ear, as well as for auditory, temperature, or chemical irritant trials.

Description

Strain Information

Type Mutant Stock; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
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Mating SystemHomozygote x Heterozygote         (Female x Male)   15-JUN-07
Specieslaboratory mouse
GenerationF6+N1F16 (11-DEC-13)
Generation Definitions
 
Donating Investigator David P. Corey,   Harvard Medical School/HHMI

Description
Homozygous mice are viable and fertile. The donating investigator reports a dramatic loss of fecundity after 5-6 months of age. The targeting vector contains an endoplasmic reticulum (ER) retention signal (KDEL), which is reported to sequester the potential truncated mRNA product in the ER. The vector also contains an IRES-PLAP reporter gene, allowing extracellular antibody staining/chromogenic development tracking of cells normally expressing the endogenous gene. Homozygous mice display behavioral deficits in response to mustard oil, cold, and punctate mechanical stimuli. These mice have a normal startle reflex to loud noise, a normal sense of balance, a normal auditory brainstem response, and normal transduction currents in vestibular hair cells. These mutants may be useful in neurobiological studies involving dorsal root ganglion neurons and cells of the inner ear, as well as for auditory, temperature, or chemical irritant trials.

Development
A "KDEL-IRES-PLAP-pA-FRT-PGKNeo-FRT" targeting vector was created with an in-frame endoplasmic reticulum (ER) retention signal and a stop codon (KDEL), internal ribosome entry site (IRES)-controlled human placental alkaline phosphatase gene (PLAP) and a polyadenylation sequence all followed by a FRT-flanked PGK-Neo cassette. This construct was designed to replace the endogenous exons encoding for the pore domain (S5 and S6 transmembrane domains and the pore loop that contains the selectivity filter). The construct was electroporated into the 129P2/OlaHsd-derived E14 embryonic stem (ES) cells. Correctly targeted ES cells (with the selection cassette removed) were injected into C57BL/6 blastocysts. Chimeric males were bred to C57BL/6 or B6129P1/F2J females. Heterozygotes were bred together and maintained on a mixed B6;129 background prior to arrival at The Jackson Laboratory.

Control Information

  Control
   100903 B6129PF2/J (approximate)
 
  Considerations for Choosing Controls

Related Strains

View Strains carrying other alleles of Trpa1     (7 strains)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI
- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested.
Episodic Pain Syndrome, Familial, 1; FEPS1   (TRPA1)
View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

Trpa1tm1Kykw/Trpa1tm1Kykw

        involves: 129P2/OlaHsd * C57BL/6J
  • behavior/neurological phenotype
  • abnormal thermosensation
    • mutants show reduced sensitivity to the cooling sensation elicited by a drop of acetone on the hindpaw compared with wild-type and heterozygotes: differences between wild-type and mutants is greater for females than males   (MGI Ref ID J:108343)
  • hyporesponsive to tactile stimuli
    • homozygous mutants are less sensitive to punctate mechanical stimuli relative to littermates; fewer mutants show a pain response than wild-type and the average threshold is higher in mutants   (MGI Ref ID J:108343)
    • 2 hours after injection with bradykinin, the threshold for mechanical sensitivity is unchanged in mutants while it is reduce 5-fold in wild-type   (MGI Ref ID J:108343)
  • increased thermal nociceptive threshold   (MGI Ref ID J:108343)
  • hearing/vestibular/ear phenotype
  • decreased threshold for auditory brainstem response
    • at frequency of 32kHz in an ABR test, mutant mice are more sensitive than wild-type, however, results are similar to controls at all other frequencies tested   (MGI Ref ID J:108343)
    • hearing and vestibular function are normal as assesed by behavioral tests   (MGI Ref ID J:108343)
    • whole-cell transduction currents in mouse utricular hair cells are similar to controls   (MGI Ref ID J:108343)
  • taste/olfaction phenotype
  • abnormal taste sensitivity
    • knockout mice consume more mustard oil-containing water than wild-type or heterozygotes; at the highest concentration, mutants consume more than one third of the normal amount   (MGI Ref ID J:108343)
  • integument phenotype
  • hyporesponsive to tactile stimuli
    • homozygous mutants are less sensitive to punctate mechanical stimuli relative to littermates; fewer mutants show a pain response than wild-type and the average threshold is higher in mutants   (MGI Ref ID J:108343)
    • 2 hours after injection with bradykinin, the threshold for mechanical sensitivity is unchanged in mutants while it is reduce 5-fold in wild-type   (MGI Ref ID J:108343)
  • increased thermal nociceptive threshold   (MGI Ref ID J:108343)
View Research Applications

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

Neurobiology Research
Behavioral and Learning Defects

Reproductive Biology Research
Fertility Defects

Research Tools
Genetics Research
      Tissue/Cell Markers
      Tissue/Cell Markers: dorsal CNS marker
      Tissue/Cell Markers: neurons
Sensorineural Research

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Trpa1tm1Kykw
Allele Name targeted mutation 1, Kelvin Y Kwan
Allele Type Targeted (Null/Knockout)
Common Name(s) Trpa1 KO;
Mutation Made By Kelvin Kwan,   Harvard Medical School/HHMI
Strain of Origin129P2/OlaHsd
ES Cell Line NameE14
ES Cell Line Strain129P2/OlaHsd
Gene Symbol and Name Trpa1, transient receptor potential cation channel, subfamily A, member 1
Chromosome 1
Gene Common Name(s) ANKTM1; FEPS;
Molecular Note The S5 and S6 transmembrane domains and the pore loop containing the selectivity filter of the gene were replaced with an IRES-PLAP-pA cassette. The resulting sequence produces a bicistronic transcript containing the 5' end of the endogenous gene followed by an independently translated human placental alkaline phosphatase gene. An endoplasmic reticulum retention signal encoded by the amino acid sequence KDEL and a stop codon were inserted in frame with the exon before the IRES-PLAP to prevent unwanted side effects from a possibly truncated product of the endogenous coding sequence. RT-PCR confirmed absence of transcript in mutants. [MGI Ref ID J:108343]

Genotyping

Genotyping Information

Genotyping Protocols

Trpa1tm1Kykw, Standard PCR
Trpa1tm1kykw, High Resolution Melting


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Kwan KY; Allchorne AJ; Vollrath MA; Christensen AP; Zhang DS; Woolf CJ; Corey DP. 2006. TRPA1 contributes to cold, mechanical, and chemical nociception but is not essential for hair-cell transduction. Neuron 50(2):277-89. [PubMed: 16630838]  [MGI Ref ID J:108343]

Additional References

Trpa1tm1Kykw related

Andersson DA; Gentry C; Bevan S. 2012. TRPA1 has a key role in the somatic pro-nociceptive actions of hydrogen sulfide. PLoS One 7(10):e46917. [PubMed: 23071662]  [MGI Ref ID J:192090]

Andersson DA; Gentry C; Light E; Vastani N; Vallortigara J; Bierhaus A; Fleming T; Bevan S. 2013. Methylglyoxal evokes pain by stimulating TRPA1. PLoS One 8(10):e77986. [PubMed: 24167592]  [MGI Ref ID J:209196]

Brierley SM; Castro J; Harrington AM; Hughes PA; Page AJ; Rychkov GY; Blackshaw LA. 2011. TRPA1 contributes to specific mechanically activated currents and sensory neuron mechanical hypersensitivity. J Physiol 589(Pt 14):3575-93. [PubMed: 21558163]  [MGI Ref ID J:189404]

Fajardo O; Meseguer V; Belmonte C; Viana F. 2008. TRPA1 channels mediate cold temperature sensing in mammalian vagal sensory neurons: pharmacological and genetic evidence. J Neurosci 28(31):7863-75. [PubMed: 18667618]  [MGI Ref ID J:139515]

Fernandes ES; Vong CT; Quek S; Cheong J; Awal S; Gentry C; Aubdool AA; Liang L; Bodkin JV; Bevan S; Heads R; Brain SD. 2013. Superoxide generation and leukocyte accumulation: key elements in the mediation of leukotriene B(4)-induced itch by transient receptor potential ankyrin 1 and transient receptor potential vanilloid 1. FASEB J 27(4):1664-73. [PubMed: 23271050]  [MGI Ref ID J:197648]

Gu Q; Lin RL. 2010. Heavy metals zinc, cadmium, and copper stimulate pulmonary sensory neurons via direct activation of TRPA1. J Appl Physiol 108(4):891-7. [PubMed: 20133428]  [MGI Ref ID J:185853]

Karashima Y; Talavera K; Everaerts W; Janssens A; Kwan KY; Vennekens R; Nilius B; Voets T. 2009. TRPA1 acts as a cold sensor in vitro and in vivo. Proc Natl Acad Sci U S A 106(4):1273-8. [PubMed: 19144922]  [MGI Ref ID J:144493]

Kwan KY; Glazer JM; Corey DP; Rice FL; Stucky CL. 2009. TRPA1 modulates mechanotransduction in cutaneous sensory neurons. J Neurosci 29(15):4808-19. [PubMed: 19369549]  [MGI Ref ID J:147955]

Lanosa MJ; Willis DN; Jordt S; Morris JB. 2010. Role of metabolic activation and the TRPA1 receptor in the sensory irritation response to styrene and naphthalene. Toxicol Sci 115(2):589-95. [PubMed: 20176620]  [MGI Ref ID J:162969]

Macpherson LJ; Xiao B; Kwan KY; Petrus MJ; Dubin AE; Hwang S; Cravatt B; Corey DP; Patapoutian A. 2007. An ion channel essential for sensing chemical damage. J Neurosci 27(42):11412-5. [PubMed: 17942735]  [MGI Ref ID J:141470]

Madrid R; de la Pena E; Donovan-Rodriguez T; Belmonte C; Viana F. 2009. Variable threshold of trigeminal cold-thermosensitive neurons is determined by a balance between TRPM8 and Kv1 potassium channels. J Neurosci 29(10):3120-31. [PubMed: 19279249]  [MGI Ref ID J:155655]

Mishra SK; Hoon MA. 2010. Ablation of TrpV1 neurons reveals their selective role in thermal pain sensation. Mol Cell Neurosci 43(1):157-63. [PubMed: 19853036]  [MGI Ref ID J:158317]

Nassini R; Pedretti P; Moretto N; Fusi C; Carnini C; Facchinetti F; Viscomi AR; Pisano AR; Stokesberry S; Brunmark C; Svitacheva N; McGarvey L; Patacchini R; Damholt AB; Geppetti P; Materazzi S. 2012. Transient receptor potential ankyrin 1 channel localized to non-neuronal airway cells promotes non-neurogenic inflammation. PLoS One 7(8):e42454. [PubMed: 22905134]  [MGI Ref ID J:189907]

Old EA; Nadkarni S; Grist J; Gentry C; Bevan S; Kim KW; Mogg AJ; Perretti M; Malcangio M. 2014. Monocytes expressing CX3CR1 orchestrate the development of vincristine-induced pain. J Clin Invest 124(5):2023-36. [PubMed: 24743146]  [MGI Ref ID J:212753]

Park CK; Xu ZZ; Berta T; Han Q; Chen G; Liu XJ; Ji RR. 2014. Extracellular microRNAs activate nociceptor neurons to elicit pain via TLR7 and TRPA1. Neuron 82(1):47-54. [PubMed: 24698267]  [MGI Ref ID J:213160]

Parra A; Madrid R; Echevarria D; del Olmo S; Morenilla-Palao C; Acosta MC; Gallar J; Dhaka A; Viana F; Belmonte C. 2010. Ocular surface wetness is regulated by TRPM8-dependent cold thermoreceptors of the cornea. Nat Med 16(12):1396-9. [PubMed: 21076394]  [MGI Ref ID J:167524]

Patil MJ; Jeske NA; Akopian AN. 2010. Transient receptor potential V1 regulates activation and modulation of transient receptor potential A1 by Ca2+. Neuroscience 171(4):1109-19. [PubMed: 20884333]  [MGI Ref ID J:170188]

Pozsgai G; Bodkin JV; Graepel R; Bevan S; Andersson DA; Brain SD. 2010. Evidence for the pathophysiological relevance of TRPA1 receptors in the cardiovascular system in vivo. Cardiovasc Res 87(4):760-8. [PubMed: 20442136]  [MGI Ref ID J:176094]

Shigetomi E; Jackson-Weaver O; Huckstepp RT; O'Dell TJ; Khakh BS. 2013. TRPA1 channels are regulators of astrocyte basal calcium levels and long-term potentiation via constitutive D-serine release. J Neurosci 33(24):10143-53. [PubMed: 23761909]  [MGI Ref ID J:199161]

Shigetomi E; Tong X; Kwan KY; Corey DP; Khakh BS. 2012. TRPA1 channels regulate astrocyte resting calcium and inhibitory synapse efficacy through GAT-3. Nat Neurosci 15(1):70-80. [PubMed: 22158513]  [MGI Ref ID J:180303]

Talavera K; Gees M; Karashima Y; Meseguer VM; Vanoirbeek JA; Damann N; Everaerts W; Benoit M; Janssens A; Vennekens R; Viana F; Nemery B; Nilius B; Voets T. 2009. Nicotine activates the chemosensory cation channel TRPA1. Nat Neurosci 12(10):1293-9. [PubMed: 19749751]  [MGI Ref ID J:154644]

Trevisan G; Hoffmeister C; Rossato MF; Oliveira SM; Silva MA; Silva CR; Fusi C; Tonello R; Minocci D; Guerra GP; Materazzi S; Nassini R; Geppetti P; Ferreira J. 2014. TRPA1 receptor stimulation by hydrogen peroxide is critical to trigger hyperalgesia and inflammation in a model of acute gout. Free Radic Biol Med 72:200-9. [PubMed: 24780252]  [MGI Ref ID J:212320]

Trevisan G; Materazzi S; Fusi C; Altomare A; Aldini G; Lodovici M; Patacchini R; Geppetti P; Nassini R. 2013. Novel Therapeutic Strategy to Prevent Chemotherapy-Induced Persistent Sensory Neuropathy By TRPA1 Blockade. Cancer Res 73(10):3120-3131. [PubMed: 23477783]  [MGI Ref ID J:197050]

Vetter I; Touska F; Hess A; Hinsbey R; Sattler S; Lampert A; Sergejeva M; Sharov A; Collins LS; Eberhardt M; Engel M; Cabot PJ; Wood JN; Vlachova V; Reeh PW; Lewis RJ; Zimmermann K. 2012. Ciguatoxins activate specific cold pain pathways to elicit burning pain from cooling. EMBO J 31(19):3795-808. [PubMed: 22850668]  [MGI Ref ID J:188624]

Vriens J; Owsianik G; Hofmann T; Philipp SE; Stab J; Chen X; Benoit M; Xue F; Janssens A; Kerselaers S; Oberwinkler J; Vennekens R; Gudermann T; Nilius B; Voets T. 2011. TRPM3 is a nociceptor channel involved in the detection of noxious heat. Neuron 70(3):482-94. [PubMed: 21555074]  [MGI Ref ID J:174798]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX10

Colony Maintenance

Breeding & HusbandryWhen maintaining a live colony, the donating investigator breeds heterozygous and homozygous mice together. Homozygous mice have some mild subfertility problems.
Mating SystemHomozygote x Heterozygote         (Female x Male)   15-JUN-07
Diet Information LabDiet® 5K52/5K67

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


Pricing for USA, Canada and Mexico shipping destinations View International Pricing

Live Mice

Price per mouse (US dollars $)GenderGenotypes Provided
Individual Mouse $239.00Female or MaleHeterozygous for Trpa1tm1Kykw  
$239.00Female or MaleHomozygous for Trpa1tm1Kykw  
Price per Pair (US dollars $)Pair Genotype
$478.00Homozygous for Trpa1tm1Kykw x Heterozygous for Trpa1tm1Kykw  

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1800 unique mouse models across a vast array of research areas. Breeding colonies provide mice for large and small orders and fluctuate in size depending on current research demand. If a strain is not immediately available, you will receive an estimated availability timeframe for your inquiry or order in 2-3 business days. Repository strains typically are delivered at 4 to 8 weeks of age. Requests for specific ages will be noted but not guaranteed and we do not accept age requests for breeder pairs. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, we will do our best to accommodate your age request.

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Live Mice

Price per mouse (US dollars $)GenderGenotypes Provided
Individual Mouse $310.70Female or MaleHeterozygous for Trpa1tm1Kykw  
$310.70Female or MaleHomozygous for Trpa1tm1Kykw  
Price per Pair (US dollars $)Pair Genotype
$621.40Homozygous for Trpa1tm1Kykw x Heterozygous for Trpa1tm1Kykw  

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1800 unique mouse models across a vast array of research areas. Breeding colonies provide mice for large and small orders and fluctuate in size depending on current research demand. If a strain is not immediately available, you will receive an estimated availability timeframe for your inquiry or order in 2-3 business days. Repository strains typically are delivered at 4 to 8 weeks of age. Requests for specific ages will be noted but not guaranteed and we do not accept age requests for breeder pairs. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, we will do our best to accommodate your age request.

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1800 unique mouse models across a vast array of research areas. Breeding colonies provide mice for large and small orders and fluctuate in size depending on current research demand. If a strain is not immediately available, you will receive an estimated availability timeframe for your inquiry or order in 2-3 business days. Repository strains typically are delivered at 4 to 8 weeks of age. Requests for specific ages will be noted but not guaranteed and we do not accept age requests for breeder pairs. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, we will do our best to accommodate your age request.

Control Information

  Control
   100903 B6129PF2/J (approximate)
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

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