Strain Name:

B6.129-Penk-rstm1Pig/J

Stock Number:

002880

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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

Type Congenic; Mutant Strain; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Additional information on Congenic nomenclature.
Specieslaboratory mouse
Background Strain C57BL/6
 
Donating InvestigatorDr. Andreas Zimmer,  

Description
Mice homozygous for the Penk-rstm1Pig targeted mutation are viable and fertile. They show an altered pain response, increased anxiety, and increased aggression. Homozygous mutants display a lower supraspinal pain threshold than wild-types; spinal pain thresholds are normal. Mutants display normal stress-induced analgesia. Note that strain background may influence phenotype.

Control Information

  Control
   000664 C57BL/6J
 
  Considerations for Choosing Controls

Related Strains

Strains carrying   Penk-rstm1Pig allele
002881   D2.129(B6)-Penk-rstm1Pig/J
View Strains carrying   Penk-rstm1Pig     (1 strain)

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

Penk-rstm1Pig/Penk-rstm1Pig

        B6.129-Penk-rstm1Pig
  • behavior/neurological phenotype
  • decreased behavioral withdrawal response
    • decrease in the severity of THC withdrawal signs (ptosis, piloerection, mastication, body tremor, paw tremor, ataxia, and hunched posture) compared to wild-type mice   (MGI Ref ID J:66732)
  • decreased chemically-elicited antinociception
    • THC induced antinociceptive response is significantly less intense in homozygotes than in wild-type mice   (MGI Ref ID J:66732)
  • homeostasis/metabolism phenotype
  • decreased physiological sensitivity to xenobiotic
    • delta9-tetrahydrocannadinol (THC) induced weight loss is reduced   (MGI Ref ID J:66732)
    • however, no difference in the effect on locomotion is seen and no difference in the induction of tolerance to THC is seen   (MGI Ref ID J:66732)
  • immune system phenotype
  • abnormal T-helper 2 physiology
    • production of IL4 and IL5 by CD4+ T cells is reduced in helminth parasite infected homozygotes   (MGI Ref ID J:62435)
    • however, levels of IgE and IgG1 in helminth parasite infected or OVA sensitized homozygotes is similar to wild type mice however, levels of IgE and IgG1 in helminth parasite infected or OVA sensitized homozygotes is similar to wild-type mice   (MGI Ref ID J:62435)
  • decreased T-helper 2 cell number
    • fewer IL5 producing CD4+ T cells are found in helminth parasite infected homozygotes; however, no difference in the number of CD4+ T cells in the lung is seen   (MGI Ref ID J:62435)
  • lung inflammation
    • OVA-sensitization and helminth parasite-induced eosinophil infiltration is reduced 2-fold compared to wild-type mice   (MGI Ref ID J:62435)
  • hematopoietic system phenotype
  • abnormal T-helper 2 physiology
    • production of IL4 and IL5 by CD4+ T cells is reduced in helminth parasite infected homozygotes   (MGI Ref ID J:62435)
    • however, levels of IgE and IgG1 in helminth parasite infected or OVA sensitized homozygotes is similar to wild type mice however, levels of IgE and IgG1 in helminth parasite infected or OVA sensitized homozygotes is similar to wild-type mice   (MGI Ref ID J:62435)
  • decreased T-helper 2 cell number
    • fewer IL5 producing CD4+ T cells are found in helminth parasite infected homozygotes; however, no difference in the number of CD4+ T cells in the lung is seen   (MGI Ref ID J:62435)
  • respiratory system phenotype
  • lung inflammation
    • OVA-sensitization and helminth parasite-induced eosinophil infiltration is reduced 2-fold compared to wild-type mice   (MGI Ref ID J:62435)
  • integument phenotype
  • decreased chemically-elicited antinociception
    • THC induced antinociceptive response is significantly less intense in homozygotes than in wild-type mice   (MGI Ref ID J:66732)

Penk-rstm1Pig/Penk-rstm1Pig

        B6.129-Penk-rstm1Pig/J
  • behavior/neurological phenotype
  • *normal* behavior/neurological phenotype
    • no difference in ethanol intake or preference is seen compared to wild type mice no difference in ethanol intake or preference is seen compared to wild-type mice   (MGI Ref ID J:107954)
    • abnormal associative learning
      • the rewarding effect of nicotine in a place-conditioning assay is reduced in homozygotes compared to wild-type mice; however, nicotine-induced decreases in locomotor activity are similar to wild-type   (MGI Ref ID J:98226)
    • decreased behavioral withdrawal response
      • the severity of nicotine withdrawal is reduced in homozygous mice   (MGI Ref ID J:98226)
    • decreased chemically-elicited antinociception
      • nicotine induced antinociceptive responses are significantly reduced in homozygotes compared to in wild-type mice   (MGI Ref ID J:98226)
    • impaired behavioral response to nicotine
      • the severity of nicotine withdrawal is reduced in homozygous mice   (MGI Ref ID J:98226)
      • the rewarding effect of nicotine in a place-conditioning assay is reduced in homozygotes compared to wild-type mice   (MGI Ref ID J:98226)
      • however, nicotine-induced decreases in locomotor activity are similar to wild-type   (MGI Ref ID J:98226)
  • homeostasis/metabolism phenotype
  • decreased physiological sensitivity to xenobiotic
    • 0.5 mg/kg nicotine significantly increases extracellular levels of dopamine in the nucleus accumbens of wild-type mice but not in homozygous mice   (MGI Ref ID J:98226)
  • integument phenotype
  • decreased chemically-elicited antinociception
    • nicotine induced antinociceptive responses are significantly reduced in homozygotes compared to in wild-type mice   (MGI Ref ID J:98226)

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

Penk-rstm1Pig/Penk-rstm1Pig

        involves: 129S1/Sv * 129X1/SvJ * CD-1
  • behavior/neurological phenotype
  • abnormal emotion/affect behavior   (MGI Ref ID J:35826)
    • decreased exploration in new environment
      • homozygotes show reduced levels of horizontal but not vertical activity during an open field test   (MGI Ref ID J:35826)
    • increased aggression toward humans
      • seen in some adults   (MGI Ref ID J:35826)
    • increased aggression towards mice
      • in a resident-intruder test, resident homozygotes are immediately aggressive towards the intruder mouse   (MGI Ref ID J:35826)
    • increased anxiety-related response
      • pups and adolescent mice display frantic running or jumping, hide under the bedding, and show prolonged freezing response to moderate noise or movement   (MGI Ref ID J:35826)
      • in an elevated O-maze, homozygotes spend less time in the open sections   (MGI Ref ID J:35826)
      • increased thigmotaxis
        • homozygotes spend more time on the edges during an open field test   (MGI Ref ID J:35826)
  • abnormal touch/ nociception   (MGI Ref ID J:35826)
    • abnormal chemical nociception
      • after formalin injection into a hind paw, homozygotes display a different suite of behaviors including, paw shaking, increased agitation, and intense sniffing, but do not lick or lift the injected paw   (MGI Ref ID J:35826)
    • decreased thermal nociceptive threshold
      • when placed on a hot plate homozygotes shake their hind paws almost immediately unlike wild-type mice   (MGI Ref ID J:35826)
      • however, analgesia induced by stress (forced swim in either 34 degree C or 4 degree C water) is similar that in wild-type mice and pain response in a tail-flick test is similar to wild-type   (MGI Ref ID J:35826)
  • reproductive system phenotype
  • *normal* reproductive system phenotype
    • homozygotes are fertile and care for their offspring   (MGI Ref ID J:35826)
  • integument phenotype
  • abnormal touch/ nociception   (MGI Ref ID J:35826)
    • abnormal chemical nociception
      • after formalin injection into a hind paw, homozygotes display a different suite of behaviors including, paw shaking, increased agitation, and intense sniffing, but do not lick or lift the injected paw   (MGI Ref ID J:35826)
    • decreased thermal nociceptive threshold
      • when placed on a hot plate homozygotes shake their hind paws almost immediately unlike wild-type mice   (MGI Ref ID J:35826)
      • however, analgesia induced by stress (forced swim in either 34 degree C or 4 degree C water) is similar that in wild-type mice and pain response in a tail-flick test is similar to wild-type   (MGI Ref ID J:35826)
View Research Applications

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

Penk-rstm1Pig related

Neurobiology Research
Behavioral and Learning Defects

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Penk-rstm1Pig
Allele Name targeted mutation 1, Pain Investigation Group
Allele Type Targeted (Null/Knockout)
Common Name(s) PPNK-; Penk KO; Penk2tm1Zim; enk-;
Mutation Made ByDr. Andreas Zimmer,  
Strain of Origin(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
ES Cell Line NameR1
ES Cell Line Strain(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
Gene Symbol and Name Penk-rs, preproenkephalin, related sequence
Chromosome 9
Gene Common Name(s) Penk; Penk2; preproenkephalin; preproenkephalin 2;
Molecular Note A PGK-neomycin resistance cassette replaced 54 bp of the 5' part of exon 3 and parts of the second intron. The mutated allele contains a rearrangement downstream from the insertion site with a partial duplication of exon 3 sequences. Northern blot analysis of brain and testis detected nearly no encoded mRNA in homozygous mice. [MGI Ref ID J:35826]

Genotyping

Genotyping Information

Genotyping Protocols

Penk-rstm1Pig, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Konig M; Zimmer AM; Steiner H; Holmes PV; Crawley JN; Brownstein MJ; Zimmer A. 1996. Pain responses, anxiety and aggression in mice deficient in pre-proenkephalin. Nature 383(6600):535-8. [PubMed: 8849726]  [MGI Ref ID J:35826]

Additional References

Penk-rstm1Pig related

Bailey A; Weber D; Zimmer A; Zimmer AM; Hourani SM; Kitchen I. 2004. Quantitative autoradiography of adenosine receptors and NBTI-sensitive adenosine transporters in the brains of mice deficient in the preproenkephalin gene. Brain Res 1025(1-2):1-9. [PubMed: 15464738]  [MGI Ref ID J:92981]

Berrendero F; Mendizabal V; Robledo P; Galeote L; Bilkei-Gorzo A; Zimmer A; Maldonado R. 2005. Nicotine-induced antinociception, rewarding effects, and physical dependence are decreased in mice lacking the preproenkephalin gene. J Neurosci 25(5):1103-12. [PubMed: 15689546]  [MGI Ref ID J:98226]

Bilkei-Gorzo A; Erk S; Schurmann B; Mauer D; Michel K; Boecker H; Scheef L; Walter H; Zimmer A. 2012. Dynorphins regulate fear memory: from mice to men. J Neurosci 32(27):9335-43. [PubMed: 22764240]  [MGI Ref ID J:185956]

Bilkei-Gorzo A; Otto M; Zimmer A. 2008. Environmental modulation of anxiety-related neuronal activity and behaviors. Behav Brain Res 186(2):289-92. [PubMed: 17904656]  [MGI Ref ID J:148659]

Bilkei-Gorzo A; Racz I; Michel K; Mauer D; Zimmer A; Klingmuller D; Zimmer A. 2008. Control of hormonal stress reactivity by the endogenous opioid system. Psychoneuroendocrinology 33(4):425-36. [PubMed: 18280051]  [MGI Ref ID J:141622]

Bilkei-Gorzo A; Racz I; Michel K; Zimmer A; Klingmuller D; Zimmer A. 2004. Behavioral phenotype of pre-proenkephalin-deficient mice on diverse congenic backgrounds. Psychopharmacology (Berl) 176(3-4):343-52. [PubMed: 15197532]  [MGI Ref ID J:103554]

Boggs DF; Miller JH. 2006. Absence of an hypoxic depression of metabolism in preproenkephalin knockout mice. Respir Physiol Neurobiol 152(1):92-9. [PubMed: 16095981]  [MGI Ref ID J:112770]

Brady LS; Herkenham M; Rothman RB; Partilla JS; Konig M; Zimmer AM; Zimmer A. 1999. Region-specific up-regulation of opioid receptor binding in enkephalin knockout mice. Brain Res Mol Brain Res 68(1-2):193-7. [PubMed: 10320798]  [MGI Ref ID J:109302]

Clarke S; Zimmer A; Zimmer AM; Hill RG; Kitchen I. 2003. Region selective up-regulation of micro-, delta- and kappa-opioid receptors but not opioid receptor-like 1 receptors in the brains of enkephalin and dynorphin knockout mice. Neuroscience 122(2):479-89. [PubMed: 14614912]  [MGI Ref ID J:126170]

Gendron L; Pintar JE; Chavkin C. 2007. Essential role of mu opioid receptor in the regulation of delta opioid receptor-mediated antihyperalgesia. Neuroscience 150(4):807-17. [PubMed: 17997230]  [MGI Ref ID J:130771]

Hook S; Camberis M; Prout M; Konig M; Zimmer A; Van Heeke G; Le Gros G. 1999. Preproenkephalin is a Th2 cytokine but is not required for Th2 differentiation in vitro. Immunol Cell Biol 77(5):385-90. [PubMed: 10540203]  [MGI Ref ID J:110538]

Hook S; Camberis M; Prout M; Le Gros G. 2003. Absence of preproenkephalin increases the threshold for T cell activation. J Neuroimmunol 140(1-2):61-8. [PubMed: 12864972]  [MGI Ref ID J:119036]

Hook S; Prout M; Camberis M; Konig M; Zimmer A; Van Heeke G; Le Gros G. 2000. Th2-dependent airway eosinophilia is regulated by preproenkephalin. J Neuroimmunol 107(1):59-65. [PubMed: 10808051]  [MGI Ref ID J:62435]

Koenig HN; Olive MF. 2002. Ethanol consumption patterns and conditioned place preference in mice lacking preproenkephalin. Neurosci Lett 325(2):75-8. [PubMed: 12044625]  [MGI Ref ID J:107954]

Mazzuca M; Heurteaux C; Alloui A; Diochot S; Baron A; Voilley N; Blondeau N; Escoubas P; Gelot A; Cupo A; Zimmer A; Zimmer AM; Eschalier A; Lazdunski M. 2007. A tarantula peptide against pain via ASIC1a channels and opioid mechanisms. Nat Neurosci 10(8):943-945. [PubMed: 17632507]  [MGI Ref ID J:123967]

Ponomarev I; Schafer GL; Blednov YA; Williams RW; Iyer VR; Harris RA. 2004. Convergent analysis of cDNA and short oligomer microarrays, mouse null mutants and bioinformatics resources to study complex traits. Genes Brain Behav 3(6):360-8. [PubMed: 15544578]  [MGI Ref ID J:104837]

Shoblock JR; Maidment NT. 2007. Enkephalin release promotes homeostatic increases in constitutively active mu opioid receptors during morphine withdrawal. Neuroscience 149(3):642-9. [PubMed: 17905519]  [MGI Ref ID J:128423]

Skoubis PD; Lam HA; Shoblock J; Narayanan S; Maidment NT. 2005. Endogenous enkephalins, not endorphins, modulate basal hedonic state in mice. Eur J Neurosci 21(5):1379-84. [PubMed: 15813947]  [MGI Ref ID J:101075]

Valverde O; Maldonado R; Valjent E; Zimmer AM; Zimmer A. 2000. Cannabinoid withdrawal syndrome is reduced in pre-proenkephalin knock-Out mice J Neurosci 20(24):9284-9. [PubMed: 11125007]  [MGI Ref ID J:66732]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

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

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* $2525.00
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.

Frozen Products

Price (US dollars $)
Frozen Embryo $1650.00

Standard Supply

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

Supply Notes

  • Cryopreserved Embryos
    Available to most shipping destinations1
    This strain is also available as cryopreserved embryos2. Orders for cryopreserved embryos may be placed with our Customer Service Department. Experienced technicians at The Jackson Laboratory have recovered frozen embryos of this strain successfully. We will provide you enough embryos to perform two embryo transfers. The Jackson Laboratory does not guarantee successful recovery at your facility. For complete information on purchasing embryos, please visit our Cryopreserved Embryos web page.

    1 Shipments cannot be made to Australia due to Australian government import restrictions.
    2 Embryos for most strains are cryopreserved at the two cell stage while some strains are cryopreserved at the eight cell stage. If this information is important to you, please contact Customer Service.
  • 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 10 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* $3283.00
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.

Frozen Products

Price (US dollars $)
Frozen Embryo $2145.00

Standard Supply

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

Supply Notes

  • Cryopreserved Embryos
    Available to most shipping destinations1
    This strain is also available as cryopreserved embryos2. Orders for cryopreserved embryos may be placed with our Customer Service Department. Experienced technicians at The Jackson Laboratory have recovered frozen embryos of this strain successfully. We will provide you enough embryos to perform two embryo transfers. The Jackson Laboratory does not guarantee successful recovery at your facility. For complete information on purchasing embryos, please visit our Cryopreserved Embryos web page.

    1 Shipments cannot be made to Australia due to Australian government import restrictions.
    2 Embryos for most strains are cryopreserved at the two cell stage while some strains are cryopreserved at the eight cell stage. If this information is important to you, please contact Customer Service.
  • 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 10 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
   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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