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; Spontaneous Mutation; 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 6 times to C57BL/6J, then two times to albino C57BL/6 mice (B6(Cg)-Tyr^c-2J/J) by the donating laboratory.

Related Strains

Strains carrying   Trpa1^tm1Kykw allele

008646	B6.129P2(Cg)-Trpa1tm1Kykw/J
006401	B6;129P-Trpa1tm1Kykw/J
008648	CBA.129P2(Cg)-Trpa1tm1Kykw/J

View Strains carrying   Trpa1^tm1Kykw     (3 strains)

Strains carrying   Tyr^c-2J allele

017614	B6(Cg)-Tyrc-2J Tg(UBC-mCherry)1Phbs/J
000058	B6(Cg)-Tyrc-2J/J
007484	B6.Cg-Tyrc-2J Tg(Tyr)3412ARpw Tg(Sry-EGFP)92Ei/EiJ

View Strains carrying   Tyr^c-2J     (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)

Strains carrying other alleles of Tyr

000090	129S1/Sv-Oca2+ Tyr+ KitlSl-J/J
000091	129T1/Sv-Oca2+ Tyrc-ch Dnd1Ter/J
005445	A.B6 Tyr+-Cybanmf333/J
005012	A.B6 Tyr+-Myo5ad-l31J/J
002565	A.B6-Tyr+/J
001017	AKXD10/TyJ
000765	AKXD13/TyJ
000954	AKXD15/TyJ
000958	AKXD16/TyJ
001093	AKXD18/TyJ
001062	AKXD21/TyJ
000947	AKXD22/TyJ
000969	AKXD24/TyJ
000777	AKXD6/TyJ
000763	AKXD9/TyJ
000409	B10.129P-H1b Hbbd Tyrc Ea7a/(5M)oSnJ
000418	B10.129P-H1b Tyrc Hbbd/(5M)nSnJ
000432	B10.C-H1b Hbbd Tyrc/(41N)SnJ
000580	B10.D2/nSn-Tyrc-4J/J
000822	B6 x 129S1/SvEi Oca2+ Tyr+-Vsx2or-J/J
000578	B6 x STOCK Tyrc-ch Bmp5se +/+ Myo6sv/J
000383	B6.C-Tyrc H1b Hbbd/ByJ
013590	B6.Cg-Braftm1Mmcm Ptentm1Hwu Tg(Tyr-cre/ERT2)13Bos/BosJ
003819	B6.Cg-Per2tm1Brd Tyrc-Brd/J
007484	B6.Cg-Tyrc-2J Tg(Tyr)3412ARpw Tg(Sry-EGFP)92Ei/EiJ
000035	B6.Cg-Tyrc-J/J
000104	B6.Cg-Tyrc-h/J
012328	B6.Cg-Tg(Tyr-cre/ERT2)13Bos/J
000054	B6.D2-Tyrc-p/J
000899	C.B6-Tyr+ Hbbs/J
000339	C3H/HeJ-Tyrc-9J/J
001294	C3H/HeJ-Tyrc-a/J
001002	C57BL/10SnJ-Tyrc-11J/J
001006	CBA/J-Tyrc-10J/J
000657	CE/J
000619	FS/EiJ
004624	FVB.129P2-Pde6b+ Tyrc-ch Fmr1tm1Cgr/J
004828	FVB.129P2-Pde6b+ Tyrc-ch/AntJ
007483	FVB.Cg-Tg(Tyr)3412ARpw Tg(Sry-EGFP)92Ei/EiJ
000494	J.Cg-Oca2+ Tyr+ Lystbg/J
002281	NFS.C58-Tyr+/J
004304	NOD.CBALs-Tyr+/LtJ
000271	SH1/LeJ
001759	STOCK A Tyrc Sha/J
000306	STOCK Dll3pu + Tyrc-ch/+ Oca2p Tyrc-ch/J
018129	STOCK Fah1R Tyrc/RJ
000006	STOCK Hk Tyrc/J
000206	STOCK a/a Tyrc-h/J

View Strains carrying other alleles of Tyr     (48 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. Albinism, Ocular, with Sensorineural Deafness   (TYR) Albinism, Oculocutaneous, Type IA; OCA1A   (TYR) Albinism, Oculocutaneous, Type IB; OCA1B   (TYR) 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

Tyr^c-2J related

Dermatology Research
Color and White Spotting Defects

Mouse/Human Gene Homologs
albinism, tyrosine negative

Sensorineural Research
Retinal Degeneration

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]
Allele Symbol		Tyrc-2J
Allele Name		albino 2 Jackson
Allele Type		Spontaneous
Strain of Origin		B6.Cg-Tyrp1 Hps1
Gene Symbol and Name		Tyr, tyrosinase
Chromosome		7
Gene Common Name(s)		C; CMM8; OCA1A; OCAIA; SHEP3; albino; c; skc35; skin/coat color 35;
Molecular Note		This mutation has a G to T base change at nucleotide 291 resulting in an amino acid change from arginine to leucine at residue 77 which lies in the highly conserved DDRE sequence. Nucleotide 291 is at the alternative 5' splice donor site for exon 1 and this allele does not produce the 1a or 1b subset of tyrosinase transcripts but does produce a significant increase in 1c and 1d transcripts. Western blots of homozygous mutant skin extracts demostrate the nearly complete absence of the broad 76-84 kDa bandof glycosylated wild-type tyrosinase. No tyrosinase activity was found in hairbulb extracts from homozygous mice. [MGI Ref ID J:36008] [MGI Ref ID J:6611]

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]

Tyr^c-2J related

Alur RP; Cox TA; Crawford MA; Gong X; Brooks BP. 2008. Optic nerve axon number in mouse is regulated by PAX2. J AAPOS 12(2):117-21. [PubMed: 18083586]  [MGI Ref ID J:172973]

Anderson MG; Hawes NL; Trantow CM; Chang B; John SW. 2008. Iris phenotypes and pigment dispersion caused by genes influencing pigmentation. Pigment Cell Melanoma Res 21(5):565-78. [PubMed: 18715234]  [MGI Ref ID J:141035]

Anderson MG; Libby RT; Mao M; Cosma IM; Wilson LA; Smith RS; John SW. 2006. Genetic context determines susceptibility to intraocular pressure elevation in a mouse pigmentary glaucoma. BMC Biol 4:20. [PubMed: 16827931]  [MGI Ref ID J:128215]

Balkema GW; Cusick K; Nguyen TH. 2001. Diurnal variation in synaptic ribbon length and visual threshold. Vis Neurosci 18(5):789-97. [PubMed: 11925014]  [MGI Ref ID J:99554]

Bravo-Nuevo A; Walsh N; Stone J. 2004. Photoreceptor degeneration and loss of retinal function in the C57BL/6-C2J mouse. Invest Ophthalmol Vis Sci 45(6):2005-12. [PubMed: 15161869]  [MGI Ref ID J:92276]

Cohen-Solal KA; Crespo-Carbone SM; Namkoong J; Mackason KR; Roberts KG; Reuhl KR; Chen S. 2002. Progressive appearance of pigmentation in amelanotic melanoma lesions. Pigment Cell Res 15(4):282-9. [PubMed: 12100494]  [MGI Ref ID J:77989]

Cortese K; Giordano F; Surace EM; Venturi C; Ballabio A; Tacchetti C; Marigo V. 2005. The ocular albinism type 1 (OA1) gene controls melanosome maturation and size. Invest Ophthalmol Vis Sci 46(12):4358-64. [PubMed: 16303920]  [MGI Ref ID J:103788]

D'Orazio JA; Nobuhisa T; Cui R; Arya M; Spry M; Wakamatsu K; Igras V; Kunisada T; Granter SR; Nishimura EK; Ito S; Fisher DE. 2006. Topical drug rescue strategy and skin protection based on the role of Mc1r in UV-induced tanning. Nature 443(7109):340-4. [PubMed: 16988713]  [MGI Ref ID J:112959]

Danciger M; Ogando D; Yang H; Matthes MT; Yu N; Ahern K; Yasumura D; Williams RW; Lavail MM. 2008. Genetic modifiers of retinal degeneration in the rd3 mouse. Invest Ophthalmol Vis Sci 49(7):2863-9. [PubMed: 18344445]  [MGI Ref ID J:136923]

Dentin R; Liu Y; Koo SH; Hedrick S; Vargas T; Heredia J; Yates J rd; Montminy M. 2007. Insulin modulates gluconeogenesis by inhibition of the coactivator TORC2. Nature 449(7160):366-9. [PubMed: 17805301]  [MGI Ref ID J:126351]

Eisenhofer G; Tian H; Holmes C; Matsunaga J; Roffler-Tarlov S; Hearing VJ. 2003. Tyrosinase: a developmentally specific major determinant of peripheral dopamine. FASEB J 17(10):1248-55. [PubMed: 12832289]  [MGI Ref ID J:119178]

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Imanishi Y; Sun W; Maeda T; Maeda A; Palczewski K. 2008. Retinyl ester homeostasis in the adipose differentiation-related protein-deficient retina. J Biol Chem 283(36):25091-102. [PubMed: 18606814]  [MGI Ref ID J:142021]

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Mitra D; Luo X; Morgan A; Wang J; Hoang MP; Lo J; Guerrero CR; Lennerz JK; Mihm MC; Wargo JA; Robinson KC; Devi SP; Vanover JC; D'Orazio JA; McMahon M; Bosenberg MW; Haigis KM; Haber DA; Wang Y; Fisher DE. 2012. An ultraviolet-radiation-independent pathway to melanoma carcinogenesis in the red hair/fair skin background. Nature 491(7424):449-53. [PubMed: 23123854]  [MGI Ref ID J:189208]

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Rosenzweig HL; Kawaguchi T; Martin TM; Planck SR; Davey MP; Rosenbaum JT. 2009. Nucleotide oligomerization domain-2 (NOD2)-induced uveitis: dependence on IFN-gamma. Invest Ophthalmol Vis Sci 50(4):1739-45. [PubMed: 19098321]  [MGI Ref ID J:146921]

Rosenzweig HL; Martin TM; Jann MM; Planck SR; Davey MP; Kobayashi K; Flavell RA; Rosenbaum JT. 2008. NOD2, the gene responsible for familial granulomatous uveitis, in a mouse model of uveitis. Invest Ophthalmol Vis Sci 49(4):1518-24. [PubMed: 18385071]  [MGI Ref ID J:136140]

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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.

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

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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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JAX^® Mice, Products & Services Conditions of Use

"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCTS" means biological materials supplied by JACKSON, and their derivatives. "RECIPIENT" means each recipient of MICE, PRODUCTS, or services provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than the internal research, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services. Acceptance of MICE or PRODUCTS from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON's prior written authorization.

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of mice, products or services, JACKSON will, at its option, provide credit or replacement for the mice or product received or the services provided.

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In no event shall JACKSON, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, PRODUCTS or services, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of JACKSON, its agents or employees. Unless prohibited by law, in purchasing or receiving MICE, PRODUCTS or services from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.

MICE and PRODUCTS are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.

The foregoing represents the General Terms and Conditions applicable to JACKSON’s MICE, PRODUCTS or services. In addition, special terms and conditions of sale of certain MICE, PRODUCTS or services may be set forth separately in JACKSON web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, PRODUCTS and services by JACKSON, and by its licensees and distributors.

Acceptance of delivery of MICE, PRODUCTS or services shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on JACKSON, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, PRODUCTS or services by JACKSON.