Strain Name:

B6;129S2-Ntrk1tm1Bbd/J

Stock Number:

002480

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Availability:

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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

Former Names TRK (A)    (Changed: 15-DEC-04 )
Type Mutant Stock; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Specieslaboratory mouse
 
Donating InvestigatorDr. Mariano Barbacid,   Centro Nacional de Investigaciones Oncol

Description
Mice homozygous for the Ntrk1tm1 targeted mutation (commonly referred to as trkA) die by 2-3 weeks of age. Homozygous mutant mice show a complete lack of both nociceptive and superior cervical ganglion neurons.

Development
Part of exons 6 and 7 of the Ntrk1 gene were replaced using a vector containing the neo resistance gene. The 129-derived D3 ES cell line was used. It has subsequently been bred to C57BL/6 mice.

Control Information

  Control
   Wild-type from the colony
   000664 C57BL/6J
 
  Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Ntrk1
022362   B6.129P2(Cg)-Ntrk1tm1Ddg/J
013720   B6.129S6(Cg)-Ntrk1tm2Ddg/J
004837   STOCK Ntrk1tm1Apat/DnJ
View Strains carrying other alleles of Ntrk1     (3 strains)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI
- Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).
Insensitivity to Pain, Congenital, with Anhidrosis; CIPA
- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested.
Thyroid Carcinoma, Familial Medullary; MTC   (NTRK1)
View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

Ntrk1tm1Bbd/Ntrk1tm1Bbd

        involves: 129S2/SvPas * C57BL/6
  • hearing/vestibular/ear phenotype
  • *normal* hearing/vestibular/ear phenotype
    • at P1, newborn homozygotes exhibit normal neuron numbers in cochlear and vestibular ganglia as well as normal innervation patterns of cochlear and vestibular sensory epithelia relative to wild-type mice   (MGI Ref ID J:41896)

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

Ntrk1tm1Bbd/Ntrk1tm1Bbd

        involves: 129S2/SvPas
  • mortality/aging
  • partial postnatal lethality
    • although normal at birth, about 50% of homozygotes die by P20   (MGI Ref ID J:17194)
  • premature death
    • no homozygotes survive beyond P55   (MGI Ref ID J:17194)
  • growth/size/body phenotype
  • decreased body size
    • at P10, homozygotes are noticeably smaller than wild-type mice   (MGI Ref ID J:17194)
  • behavior/neurological phenotype
  • abnormal vibrissae reflex
    • at P10, homozygotes fail to orient in response to vibrissal stimulation   (MGI Ref ID J:17194)
  • increased thermal nociceptive threshold
    • at P10, homozygotes remain on a hot plate at 60 degrees Celsius for at least 10 sec, whereas wild-type and heterozygous mice jump off within 1-2 sec   (MGI Ref ID J:17194)
  • unresponsive to tactile stimuli
    • at p10, homozygotes fail to react to deep pinpricks in the their whisker pads and rear paws   (MGI Ref ID J:17194)
  • nervous system phenotype
  • abnormal cholinergic neuron morphology
    • adult homozygotes display a reduction in the cholinergic basal forebrain projections to the hippocampus and cerebral cortex   (MGI Ref ID J:17194)
  • abnormal sympathetic ganglion morphology
    • at P0, a number of sympathetic ganglia display neuronal loss   (MGI Ref ID J:17194)
    • small superior cervical ganglion
      • at P0, superior cervical ganglia (SCG) show neuronal loss as well as pyknotic nuclei, suggesting cellular degeneration   (MGI Ref ID J:17194)
      • by P10, the SGC is severely shrunken   (MGI Ref ID J:17194)
  • abnormal sympathetic nervous system physiology
    • upon eye illumination, the iris constricts without efficient redilation, indicating that the parasympathetic component of the oculomotor nerve is intact but the sympathetic innervation from the superior cervical ganglion is defective   (MGI Ref ID J:17194)
    • in contrast, the facial, acoustic and glossopharyngeal nerves function normally   (MGI Ref ID J:17194)
  • small dorsal root ganglion
    • at P0, dorsal root ganglia show a 70-90% loss of neurons; small-sized neurons are preferentially lost   (MGI Ref ID J:17194)
  • small trigeminal ganglion
    • at P0, trigeminal ganglia are significantly smaller and the number of trigeminal neurons is reduced by 70-90%   (MGI Ref ID J:17194)
    • other cranial ganglia appear normal   (MGI Ref ID J:17194)
  • pigmentation phenotype
  • mottled coat
    • at >3-4 weeks of age, homozygotes display a mottled fur   (MGI Ref ID J:17194)
  • vision/eye phenotype
  • blepharoptosis
    • by P20, surviving homozygotes exhibit slight ptosis   (MGI Ref ID J:17194)
  • corneal opacity
    • at >3-4 weeks, corneal opacities are observed   (MGI Ref ID J:17194)
  • miotic pupils
    • by P20, surviving homozygotes have myotic pupils   (MGI Ref ID J:17194)
  • limbs/digits/tail phenotype
  • abnormal digit morphology
    • at >3-4 weeks, digits are missing, probably due to self-mutilation   (MGI Ref ID J:17194)
  • ulcerated paws
    • at >3-4 weeks, homozygotes display ulcerated paws   (MGI Ref ID J:17194)
  • integument phenotype
  • increased thermal nociceptive threshold
    • at P10, homozygotes remain on a hot plate at 60 degrees Celsius for at least 10 sec, whereas wild-type and heterozygous mice jump off within 1-2 sec   (MGI Ref ID J:17194)
  • mottled coat
    • at >3-4 weeks of age, homozygotes display a mottled fur   (MGI Ref ID J:17194)
  • skin lesions
    • at >3-4 weeks of age, homozygotes develop multiple scabs all over their body   (MGI Ref ID J:17194)
  • unresponsive to tactile stimuli
    • at p10, homozygotes fail to react to deep pinpricks in the their whisker pads and rear paws   (MGI Ref ID J:17194)

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Ntrk1tm1Bbd
Allele Name targeted mutation 1, Mariano Barbacid
Allele Type Targeted (knock-out)
Common Name(s) trkTK; trkA-; trkAK-;
Mutation Made ByDr. Mariano Barbacid,   Centro Nacional de Investigaciones Oncol
Strain of Origin129S2/SvPas
ES Cell Line NameD3
ES Cell Line Strain129S2/SvPas
Gene Symbol and Name Ntrk1, neurotrophic tyrosine kinase, receptor, type 1
Chromosome 3
Gene Common Name(s) C80751; MTC; TRK; TRK1; TRKA; Tkr; Trk-A; expressed sequence C80751; p140-TrkA; tyrosine kinase receptor proto-oncogene;
Molecular Note Sequences encoding 51 amino acids of the kinase catalytic domain were replaced with a neomycin cassette. RNase protection analysis on tissues isolated from homozygous mutant mice failed to identify any Ntrk1 transcripts. [MGI Ref ID J:17194]

Genotyping

Genotyping Information

Genotyping Protocols

Ntrk1tm1Bbd, Separated PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Smeyne RJ; Klein R; Schnapp A; Long LK; Bryant S; Lewin A; Lira SA; Barbacid M. 1994. Severe sensory and sympathetic neuropathies in mice carrying a disrupted Trk/NGF receptor gene [see comments] Nature 368(6468):246-9. [PubMed: 8145823]  [MGI Ref ID J:17194]

Additional References

Fagan AM; Zhang H; Landis S; Smeyne RJ; Silos-Santiago I; Barbacid M. 1996. TrkA, but not TrkC, receptors are essential for survival of sympathetic neurons in vivo. J Neurosci 16(19):6208-18. [PubMed: 8815902]  [MGI Ref ID J:35563]

Silos-Santiago I; Molliver DC; Ozaki S; Smeyne RJ; Fagan AM; Barbacid M; Snider WD. 1995. Non-TrkA-expressing small DRG neurons are lost in TrkA deficient mice. J Neurosci 15(9):5929-42. [PubMed: 7666178]  [MGI Ref ID J:28575]

White FA; Silos-Santiago I; Molliver DC; Nishimura M; Phillips H; Barbacid M; Snider WD. 1996. Synchronous onset of NGF and TrkA survival dependence in developing dorsal root ganglia. J Neurosci 16(15):4662-72. [PubMed: 8764654]  [MGI Ref ID J:34321]

Ntrk1tm1Bbd related

Andres R; Herraez-Baranda LA; Thompson J; Wyatt S; Davies AM. 2008. Regulation of sympathetic neuron differentiation by endogenous nerve growth factor and neurotrophin-3. Neurosci Lett 431(3):241-6. [PubMed: 18162309]  [MGI Ref ID J:141631]

Bourane S; Garces A; Venteo S; Pattyn A; Hubert T; Fichard A; Puech S; Boukhaddaoui H; Baudet C; Takahashi S; Valmier J; Carroll P. 2009. Low-threshold mechanoreceptor subtypes selectively express MafA and are specified by Ret signaling. Neuron 64(6):857-70. [PubMed: 20064392]  [MGI Ref ID J:157721]

Cronk KM; Wilkinson GA; Grimes R; Wheeler EF; Jhaveri S; Fundin BT; Silos-Santiago I; Tessarollo L; Reichardt LF; Rice FL. 2002. Diverse dependencies of developing Merkel innervation on the trkA and both full-length and truncated isoforms of trkC. Development 129(15):3739-50. [PubMed: 12117822]  [MGI Ref ID J:77445]

Fagan AM; Garber M; Barbacid M; Silos-Santiago I; Holtzman DM. 1997. A role for TrkA during maturation of striatal and basal forebrain cholinergic neurons in vivo. J Neurosci 17(20):7644-54. [PubMed: 9315886]  [MGI Ref ID J:43471]

Fagan AM; Zhang H; Landis S; Smeyne RJ; Silos-Santiago I; Barbacid M. 1996. TrkA, but not TrkC, receptors are essential for survival of sympathetic neurons in vivo. J Neurosci 16(19):6208-18. [PubMed: 8815902]  [MGI Ref ID J:35563]

Fundin BT; Silos-Santiago I; Ernfors P; Fagan AM; Aldskogius H ; DeChiara TM ; Phillips HS ; Barbacid M ; Yancopoulos GD ; Rice FL. 1997. Differential dependency of cutaneous mechanoreceptors on neurotrophins, trk receptors, and P75 LNGFR. Dev Biol 190(1):94-116. [PubMed: 9331334]  [MGI Ref ID J:43425]

Garcia-Suarez O; Germana A; Hannestad J; Ciriaco E; Laura R; Naves J; Esteban I; Silos-Santiago I; Vega JA. 2000. TrkA is necessary for the normal development of the murine thymus. J Neuroimmunol 108(1-2):11-21. [PubMed: 10900332]  [MGI Ref ID J:102970]

Ichikawa H; Matsuo S; Silos-Santiago I; Jacquin MF; Sugimoto T. 2001. Developmental dependency of Merkel endings on trks in the palate. Brain Res Mol Brain Res 88(1-2):171-5. [PubMed: 11295244]  [MGI Ref ID J:109307]

Ichikawa H; Matsuo S; Silos-Santiago I; Jacquin MF; Sugimoto T. 2004. The development of myelinated nociceptors is dependent upon trks in the trigeminal ganglion. Acta Histochem 106(5):337-43. [PubMed: 15530548]  [MGI Ref ID J:101950]

Ichikawa H; Matsuo S; Silos-Santiago I; Sugimoto T. 2000. Developmental dependency of Meissner corpuscles on trkB but not trkA or trkC Neuroreport 11(2):259-62. [PubMed: 10674466]  [MGI Ref ID J:60480]

Matsuo S; Ichikawa H; Henderson TA; Silos-Santiago I; Barbacid M; Arends JJ; Jacquin MF. 2001. trkA modulation of developing somatosensory neurons in oro-facial tissues: tooth pulp fibers are absent in trkA knockout mice. Neuroscience 105(3):747-60. [PubMed: 11516838]  [MGI Ref ID J:85913]

Middleton G; Davies AM. 2001. Populations of NGF-dependent neurones differ in their requirement for BAX to undergo apoptosis in the absence of NGF/TrkA signalling in vivo. Development 128(23):4715-28. [PubMed: 11731452]  [MGI Ref ID J:72722]

Minichiello L; Klein R. 1996. TrkB and TrkC neurotrophin receptors cooperate in promoting survival of hippocampal and cerebellar granule neurons. Genes Dev 10(22):2849-58. [PubMed: 8918886]  [MGI Ref ID J:36756]

Minichiello L; Piehl F; Vazquez E; Schimmang T; Hokfelt T; Represa J; Klein R. 1995. Differential effects of combined trk receptor mutations on dorsal root ganglion and inner ear sensory neurons. Development 121(12):4067-75. [PubMed: 8575307]  [MGI Ref ID J:30344]

Patel TD; Jackman A; Rice FL; Kucera J; Snider WD. 2000. Development of sensory neurons in the absence of NGF/TrkA signaling in vivo [see comments] Neuron 25(2):345-57. [PubMed: 10719890]  [MGI Ref ID J:60772]

Pinon LG; Minichiello L; Klein R; Davies AM. 1996. Timing of neuronal death in trkA, trkB and trkC mutant embryos reveals developmental changes in sensory neuron dependence on Trk signalling. Development 122(10):3255-61. [PubMed: 8898237]  [MGI Ref ID J:36236]

Rice FL; Albers KM; Davis BM; Silos-Santiago I; Wilkinson GA; LeMaster AM; Ernfors P; Smeyne RJ; Aldskogius H; Phillips HS; Barbacid M; DeChiara TM; Yancopoulos GD; Dunne CE; Fundin BT. 1998. Differential dependency of unmyelinated and A delta epidermal and upper dermal innervation on neurotrophins, trk receptors, and p75LNGFR. Dev Biol 198(1):57-81. [PubMed: 9640332]  [MGI Ref ID J:107715]

Schimmang T; Alvarez-Bolado G; Minichiello L; Vazquez E; Giraldez F ; Klein R ; Represa J. 1997. Survival of inner ear sensory neurons in trk mutant mice. Mech Dev 64(1-2):77-85. [PubMed: 9232598]  [MGI Ref ID J:41896]

Schober A; Minichiello L; Keller M; Huber K; Layer PG; Roig-Lopez JL ; Garcia-Arraras JE ; Klein R ; Unsicker K. 1997. Reduced acetylcholinesterase (AChE) activity in adrenal medulla and loss of sympathetic preganglionic neurons in TrkA-deficient, but not TrkB-deficient, mice. J Neurosci 17(3):891-903. [PubMed: 8994044]  [MGI Ref ID J:38394]

Sedy J; Szeder V; Walro JM; Ren ZG; Nanka O; Tessarollo L; Sieber-Blum M; Grim M; Kucera J. 2004. Pacinian corpuscle development involves multiple Trk signaling pathways. Dev Dyn 231(3):551-63. [PubMed: 15376326]  [MGI Ref ID J:93853]

Silos-Santiago I; Molliver DC; Ozaki S; Smeyne RJ; Fagan AM; Barbacid M; Snider WD. 1995. Non-TrkA-expressing small DRG neurons are lost in TrkA deficient mice. J Neurosci 15(9):5929-42. [PubMed: 7666178]  [MGI Ref ID J:28575]

Vaegter CB; Jansen P; Fjorback AW; Glerup S; Skeldal S; Kjolby M; Richner M; Erdmann B; Nyengaard JR; Tessarollo L; Lewin GR; Willnow TE; Chao MV; Nykjaer A. 2011. Sortilin associates with Trk receptors to enhance anterograde transport and neurotrophin signaling. Nat Neurosci 14(1):54-61. [PubMed: 21102451]  [MGI Ref ID J:170255]

White FA; Silos-Santiago I; Molliver DC; Nishimura M; Phillips H; Barbacid M; Snider WD. 1996. Synchronous onset of NGF and TrkA survival dependence in developing dorsal root ganglia. J Neurosci 16(15):4662-72. [PubMed: 8764654]  [MGI Ref ID J:34321]

de Castro F; Silos-Santiago I; Lopez de Armentia M; Barbacid M; Belmonte C. 1998. Corneal innervation and sensitivity to noxious stimuli in trkA knockout mice. Eur J Neurosci 10(1):146-52. [PubMed: 9753121]  [MGI Ref ID J:89430]

von Bohlen und Halbach O; Minichiello L; Unsicker K. 2005. Haploin-sufficiency for trkB and trkC receptors induces cell loss and accumulation of alpha-synuclein in the substantia nigra. FASEB J 19(12):1740-2. [PubMed: 16037097]  [MGI Ref ID J:102679]

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 & HusbandryWhen maintaining a live colony, this mutant can be maintained by mating heterozygous siblings or by mating heterozygous mice with normal wildtype siblings. Homozygous mice die by 2-3 weeks of age.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


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

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $3175.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.
    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 11 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice
    Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $4127.50
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.
    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 11 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice
    Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Control Information

  Control
   Wild-type from the colony
   000664 C57BL/6J
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

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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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