Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Type Congenic; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Species laboratory mouse   Donating Investigator David P. Corey,   Harvard Medical School/HHMI

Description
Exons encoding the pore domain of the transient receptor potential cation channel, subfamily A, member 1 gene were deleted in this targeted mutation strain. Animals show reduced sensitivity to pain. RT-PCR of dorsal root ganglia confirmed the absence of mRNA in homozygous mutant mice. Homozygotes are viable and fertile.

Development
A targeting vector was created to replace exons 21-24 (encoding the pore forming domain of the gene) with an endoplasmic reticulum retention signal (peptide KDEL), an internal ribosome entry site (IRES), a human placental alkaline phosphatase gene (PLAP), and a polyadenylation sequence (pA) followed by an FRT-flanked neomycin resistance cassette. The mutation was created in 129P2/OlaHsd-derived E14.1 embryonic stem (ES) cells. The neomycin cassette was excised by crossing the mice with an FLP strain directed by a Gt(ROSA)26Sor promoter on an unknown genetic background. FLP was selectively bred away from the strain. This line was backcrossed 10 times to C57BL/6J by the donating laboratory.

Related Strains

Strains carrying   Trpa1^tm1Kykw allele

008647	B6.129P2(Cg)-Trpa1tm1Kykw Tyrc-2J/J
006401	B6;129P-Trpa1tm1Kykw/J
008648	CBA.129P2(Cg)-Trpa1tm1Kykw/J

View Strains carrying   Trpa1^tm1Kykw     (3 strains)

Strains carrying other alleles of Trpa1

008649	129S-Trpa1tm2Kykw/J
008650	B6.129S-Trpa1tm2Kykw/J
008654	STOCK Trpa1tm2.1Kykw/J
008813	STOCK Trpa1tm2Kykw Tg(CAG-cre/Esr1*)5Amc/J

View Strains carrying other alleles of Trpa1     (4 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; FEPS   (TRPA1)

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Trpa1^tm1Kykw/Trpa1^tm1Kykw

        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

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 (knock-out)
Common Name(s)		Trpa1 KO;
Mutation Made By		Kelvin Kwan,   Harvard Medical School/HHMI
Strain of Origin		129P2/OlaHsd
ES Cell Line Name		E14
ES Cell Line Strain		129P2/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

(Cg)-Trpa1^tm1Kykw, Standard PCR

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

Trpa1^tm1Kykw 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]

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]

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]

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; 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]

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

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Health & Colony Maintenance Information

Animal Health Reports

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

Colony Maintenance

Breeding & Husbandry	When maintained as a live colony, homozygotes may be bred.

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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.

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