Strain Name:

B6;129S6-Ppp3cbtm1Jmk/J

Stock Number:

009066

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Homozygous targeted Ppp3cb (protein phosphatase 3, catalytic subunit, beta isoform) mice show a dramatically impaired ability to generate a hypertrophic response induced by pressure overload, angiotensin II infusion, or isoproterenol infusion. Impaired T cell development and a reduced number of peripheral T cell numbers with defective proliferative capacity are also seen. These mice are permissive to allogeneic tumor cell tranplantation in vivo. Increased locomotor activity and impaired working memory are also characteristic of these mice.

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 Mutant Stock; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Specieslaboratory mouse
 
Donating Investigator Jeffery D. Molkentin,   Cincinnati Children's Hospital

Description
Homozyous mice display an 80% decrease in calcineurin enzymatic activity in the heart that is associated with a 12% reduction in basal heart size. Mice show a dramatically impaired ability to generate a hypertrophic response induced by pressure overload, angiotensin II infusion, or isoproterenol infusion. Impaired T cell development and a reduced number of peripheral T cell numbers with defective proliferative capacity are also seen. These mice are permissive to allogeneic tumor cell tranplantation in vivo. Increased locomotor activity and impaired working memory are also characteristic of these mice. Homozygous targeted mutation mice are viable, fertile, and overtly normal well into adulthood. This strain may be useful in studies of cardiac hypertrophic growth, immunodeficiency, and behavioral studies.

Development
Exon 2, encoding a catalytic domain, was replaced by a neomycin resistance cassette using KG1 129S6/SvEvTac-derived embryonic stem cells. Chimera's were crossed to C57BL/6 and the strain was maintained on a mixed C57BL/6 and 129S6 genetic background by the donating laboratory.

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

Ppp3cbtm1Jmk/Ppp3cbtm1Jmk

        involves: 129S6/SvEvTac * C57BL/6
  • cardiovascular system phenotype
  • *normal* cardiovascular system phenotype
    • normal cardiovascular function   (MGI Ref ID J:75775)
    • normal fractional shortening   (MGI Ref ID J:75775)
    • normal heart rate   (MGI Ref ID J:75775)
    • normal mean arterial blood pressure   (MGI Ref ID J:75775)
    • normal angiotensin II-induced pressor response   (MGI Ref ID J:75775)
    • decreased response of heart to induced stress
      • inability to mount hypertrophic response to pressure overload, angiotensin II infusion, or isoproterenol infusion   (MGI Ref ID J:75775)
    • small heart
      • 12% reduction in basal heart size, with trend toward smaller chamber dimensions, ventricular wall thickness, and septal wall thickness   (MGI Ref ID J:75775)
  • growth/size/body phenotype
  • decreased body weight
    • male mice showed 10% reduction in body weight at 8 weeks of age   (MGI Ref ID J:75775)
  • hematopoietic system phenotype
  • abnormal T cell differentiation   (MGI Ref ID J:77729)
    • decreased T cell proliferation
      • in response to either CD3-activating antibodies or PMA/ionomycin   (MGI Ref ID J:77729)
  • decreased T cell number
    • of total peripheral T cells   (MGI Ref ID J:77729)
    • decreased single-positive T cell number
      • reduced numbers of CD3+, and CD4 and CD8 single positive T cells   (MGI Ref ID J:77729)
  • decreased thymus weight   (MGI Ref ID J:75775)
  • thymus hypoplasia
    • evident between 4 and 8 weeks of age   (MGI Ref ID J:77729)
  • immune system phenotype
  • abnormal T cell differentiation   (MGI Ref ID J:77729)
    • decreased T cell proliferation
      • in response to either CD3-activating antibodies or PMA/ionomycin   (MGI Ref ID J:77729)
  • decreased T cell number
    • of total peripheral T cells   (MGI Ref ID J:77729)
    • decreased single-positive T cell number
      • reduced numbers of CD3+, and CD4 and CD8 single positive T cells   (MGI Ref ID J:77729)
  • decreased thymus weight   (MGI Ref ID J:75775)
  • thymus hypoplasia
    • evident between 4 and 8 weeks of age   (MGI Ref ID J:77729)
  • homeostasis/metabolism phenotype
  • decreased response of heart to induced stress
    • inability to mount hypertrophic response to pressure overload, angiotensin II infusion, or isoproterenol infusion   (MGI Ref ID J:75775)

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

Ppp3cbtm1Jmk/Ppp3cbtm1Jmk

        involves: 129S6/SvEvTac
  • immune system phenotype
  • abnormal cytokine secretion
    • in response to stimulation, total splenocytes show increased Il2 production compared to wild-type   (MGI Ref ID J:109586)
  • decreased T cell proliferation
    • in response to stimulation, total splenocytes show reduced proliferation   (MGI Ref ID J:109586)
  • homeostasis/metabolism phenotype
  • decreased susceptibility to injury
    • cardiac function reveals partial protection from pressure overload stimulation decompensation induced by transverse aortic constriction compared to wild-type; cardiac hypertrophy is attenuated   (MGI Ref ID J:109586)
  • muscle phenotype
  • abnormal skeletal muscle fiber type ratio
    • the skeletal muscle exhibits less oxidative/slow fiber muscle type than wild-type   (MGI Ref ID J:110822)
  • decreased skeletal muscle fiber diameter
    • the cross-sectional area of the soleus is decreased   (MGI Ref ID J:110822)
    • the cross-sectional area in the extensor digitorum longus is normal   (MGI Ref ID J:110822)
  • increased skeletal muscle fiber number
    • the number of fibers is increased in the soleus   (MGI Ref ID J:110822)
    • the fiber number in the extensor digitorum longus is normal   (MGI Ref ID J:110822)
  • growth/size/body phenotype
  • decreased body weight
    • mice exhibit reduced body weight despite normal muscle weights for their size (27.0+/-1.0 g compared to 30.3+/-0.7 g in wild-type mice)   (MGI Ref ID J:110822)
  • hematopoietic system phenotype
  • decreased T cell proliferation
    • in response to stimulation, total splenocytes show reduced proliferation   (MGI Ref ID J:109586)
View Research Applications

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

Cardiovascular Research
Heart Abnormalities

Immunology, Inflammation and Autoimmunity Research
Immunodeficiency
      T cell deficiency

Neurobiology Research
Behavioral and Learning Defects

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Ppp3cbtm1Jmk
Allele Name targeted mutation 1, Jeffery D Molkentin
Allele Type Targeted (knock-out)
Common Name(s) Abeta-; CnAbeta KO; CnAbeta-; Cnab-;
Mutation Made By Jeffery Molkentin,   Cincinnati Children's Hospital
Strain of Origin129S6/SvEvTac
ES Cell Line NameKG-1
ES Cell Line Strain129S6/SvEvTac
Gene Symbol and Name Ppp3cb, protein phosphatase 3, catalytic subunit, beta isoform
Chromosome 14
Gene Common Name(s) 1110063J16Rik; CALNA2; CALNB; CNA2; Calnb; CnAbeta; Cnab; PP2BA beta; PP2Bbeta; RIKEN cDNA 1110063J16 gene; calcineurin, beta subunit;
Molecular Note The exon encoding the catalytic domain of the protein was replaced with a neomycin resistance cassette via homologous recombination. Western blot analysis confirmed the absence of gene expression in brain of homozygous mutant animals. [MGI Ref ID J:75775]

Genotyping

Genotyping Information

Genotyping Protocols

Ppp3cbtm1Jmk STD PCR, Separated PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Bueno OF; Wilkins BJ; Tymitz KM; Glascock BJ; Kimball TF; Lorenz JN; Molkentin JD. 2002. Impaired cardiac hypertrophic response in Calcineurin Abeta -deficient mice. Proc Natl Acad Sci U S A 99(7):4586-91. [PubMed: 11904392]  [MGI Ref ID J:75775]

Additional References

Ppp3cbtm1Jmk related

Braz JC; Bueno OF; Liang Q; Wilkins BJ; Dai YS; Parsons S; Braunwart J; Glascock BJ; Klevitsky R; Kimball TF; Hewett TE; Molkentin JD. 2003. Targeted inhibition of p38 MAPK promotes hypertrophic cardiomyopathy through upregulation of calcineurin-NFAT signaling. J Clin Invest 111(10):1475-86. [PubMed: 12750397]  [MGI Ref ID J:83547]

Bueno OF; Brandt EB; Rothenberg ME; Molkentin JD. 2002. Defective T cell development and function in calcineurin A beta -deficient mice. Proc Natl Acad Sci U S A 99(14):9398-403. [PubMed: 12091710]  [MGI Ref ID J:77729]

Bueno OF; Lips DJ; Kaiser RA; Wilkins BJ; Dai YS; Glascock BJ; Klevitsky R; Hewett TE; Kimball TR; Aronow BJ; Doevendans PA; Molkentin JD. 2004. Calcineurin Abeta gene targeting predisposes the myocardium to acute ischemia-induced apoptosis and dysfunction. Circ Res 94(1):91-9. [PubMed: 14615291]  [MGI Ref ID J:95259]

Doetschman T; Sholl A; Chen HD; Gard C; Hildeman DA; Bommireddy R. 2011. Divergent effects of calcineurin Abeta on regulatory and conventional T-cell homeostasis. Clin Immunol 138(3):321-30. [PubMed: 21256088]  [MGI Ref ID J:169414]

Donaldson C; Eder S; Baker C; Aronovitz MJ; Weiss AD; Hall-Porter M; Wang F; Ackerman A; Karas RH; Molkentin JD; Patten RD. 2009. Estrogen attenuates left ventricular and cardiomyocyte hypertrophy by an estrogen receptor-dependent pathway that increases calcineurin degradation. Circ Res 104(2):265-75, 11p following 275. [PubMed: 19074476]  [MGI Ref ID J:156429]

Gooch JL; Toro JJ; Guler RL; Barnes JL. 2004. Calcineurin A-alpha but not A-beta is required for normal kidney development and function. Am J Pathol 165(5):1755-65. [PubMed: 15509543]  [MGI Ref ID J:93625]

Heineke J; Auger-Messier M; Correll RN; Xu J; Benard MJ; Yuan W; Drexler H; Parise LV; Molkentin JD. 2010. CIB1 is a regulator of pathological cardiac hypertrophy. Nat Med 16(8):872-9. [PubMed: 20639889]  [MGI Ref ID J:163320]

Hsu S; Nagayama T; Koitabashi N; Zhang M; Zhou L; Bedja D; Gabrielson KL; Molkentin JD; Kass DA; Takimoto E. 2009. Phosphodiesterase 5 inhibition blocks pressure overload-induced cardiac hypertrophy independent of the calcineurin pathway. Cardiovasc Res 81(2):301-9. [PubMed: 19029137]  [MGI Ref ID J:162202]

Kulkarni RM; Greenberg JM; Akeson AL. 2009. NFATc1 regulates lymphatic endothelial development. Mech Dev 126(5-6):350-65. [PubMed: 19233265]  [MGI Ref ID J:149253]

Liu H; Ye W; Guan G; Dong Z; Jia Z; Yang T. 2007. Developmental regulation of calcineurin isoforms in the rodent kidney: association with COX-2. Am J Physiol Renal Physiol 293(6):F1898-904. [PubMed: 17881460]  [MGI Ref ID J:127529]

Liu Q; Sargent MA; York AJ; Molkentin JD. 2009. ASK1 regulates cardiomyocyte death but not hypertrophy in transgenic mice. Circ Res 105(11):1110-7. [PubMed: 19815822]  [MGI Ref ID J:170149]

Madsen K; Friis UG; Gooch JL; Hansen PB; Holmgaard L; Skott O; Jensen BL. 2010. Inhibition of calcineurin phosphatase promotes exocytosis of renin from juxtaglomerular cells. Kidney Int 77(2):110-7. [PubMed: 19907416]  [MGI Ref ID J:172545]

Manicassamy S; Gupta S; Huang Z; Molkentin JD; Shang W; Sun Z. 2008. Requirement of calcineurin a for the survival of naive T cells. J Immunol 180(1):106-12. [PubMed: 18097009]  [MGI Ref ID J:130898]

Moz Y; Levi R; Lavi-Moshayoff V; Cox KB; Molkentin JD; Silver J; Naveh-Many T. 2004. Calcineurin Abeta is central to the expression of the renal type II Na/Pi co-transporter gene and to the regulation of renal phosphate transport. J Am Soc Nephrol 15(12):2972-80. [PubMed: 15579499]  [MGI Ref ID J:103718]

Muili KA; Ahmad M; Orabi AI; Mahmood SM; Shah AU; Molkentin JD; Husain SZ. 2012. Pharmacological and genetic inhibition of calcineurin protects against carbachol-induced pathological zymogen activation and acinar cell injury. Am J Physiol Gastrointest Liver Physiol 302(8):G898-905. [PubMed: 22323127]  [MGI Ref ID J:185380]

Nakayama H; Wilkin BJ; Bodi I; Molkentin JD. 2006. Calcineurin-dependent cardiomyopathy is activated by TRPC in the adult mouse heart. FASEB J 20(10):1660-70. [PubMed: 16873889]  [MGI Ref ID J:111510]

Parsons SA; Millay DP; Sargent MA; Naya FJ; McNally EM; Sweeney HL; Molkentin JD. 2007. Genetic disruption of calcineurin improves skeletal muscle pathology and cardiac disease in a mouse model of limb-girdle muscular dystrophy. J Biol Chem 282(13):10068-78. [PubMed: 17289669]  [MGI Ref ID J:121162]

Parsons SA; Millay DP; Wilkins BJ; Bueno OF; Tsika GL; Neilson JR; Liberatore CM; Yutzey KE; Crabtree GR; Tsika RW; Molkentin JD. 2004. Genetic loss of calcineurin blocks mechanical overload-induced skeletal muscle fiber type switching but not hypertrophy. J Biol Chem 279(25):26192-200. [PubMed: 15082723]  [MGI Ref ID J:91040]

Parsons SA; Wilkins BJ; Bueno OF; Molkentin JD. 2003. Altered skeletal muscle phenotypes in calcineurin Aalpha and Abeta gene-targeted mice. Mol Cell Biol 23(12):4331-43. [PubMed: 12773574]  [MGI Ref ID J:110822]

Roberts-Wilson TK; Reddy RN; Bailey JL; Zheng B; Ordas R; Gooch JL; Price SR. 2010. Calcineurin signaling and PGC-1alpha expression are suppressed during muscle atrophy due to diabetes. Biochim Biophys Acta 1803(8):960-7. [PubMed: 20359506]  [MGI Ref ID J:165376]

Sanna B; Brandt EB; Kaiser RA; Pfluger P; Witt SA; Kimball TR; van Rooij E; De Windt LJ; Rothenberg ME; Tschop MH; Benoit SC; Molkentin JD. 2006. Modulatory calcineurin-interacting proteins 1 and 2 function as calcineurin facilitators in vivo. Proc Natl Acad Sci U S A 103(19):7327-32. [PubMed: 16648267]  [MGI Ref ID J:109586]

Sanna B; Bueno OF; Dai YS; Wilkins BJ; Molkentin JD. 2005. Direct and indirect interactions between calcineurin-NFAT and MEK1-extracellular signal-regulated kinase 1/2 signaling pathways regulate cardiac gene expression and cellular growth. Mol Cell Biol 25(3):865-78. [PubMed: 15657416]  [MGI Ref ID J:95999]

Suk HY; Zhou C; Yang TT; Zhu H; Yu RY; Olabisi O; Yang X; Brancho D; Kim JY; Scherer PE; Frank PG; Lisanti MP; Calvert JW; Lefer DJ; Molkentin JD; Ghigo A; Hirsch E; Jin J; Chow CW. 2013. Ablation of calcineurin Abeta reveals hyperlipidemia and signaling cross-talks with phosphodiesterases. J Biol Chem 288(5):3477-88. [PubMed: 23258544]  [MGI Ref ID J:195655]

Sun T; Wu XS; Xu J; McNeil BD; Pang ZP; Yang W; Bai L; Qadri S; Molkentin JD; Yue DT; Wu LG. 2010. The role of calcium/calmodulin-activated calcineurin in rapid and slow endocytosis at central synapses. J Neurosci 30(35):11838-47. [PubMed: 20810903]  [MGI Ref ID J:164000]

Wu X; Chang B; Blair NS; Sargent M; York AJ; Robbins J; Shull GE; Molkentin JD. 2009. Plasma membrane Ca2+-ATPase isoform 4 antagonizes cardiac hypertrophy in association with calcineurin inhibition in rodents. J Clin Invest 119(4):976-85. [PubMed: 19287093]  [MGI Ref ID J:149624]

Yamaguchi N; Chakraborty A; Pasek DA; Molkentin JD; Meissner G. 2011. Dysfunctional ryanodine receptor and cardiac hypertrophy: role of signaling molecules. Am J Physiol Heart Circ Physiol :. [PubMed: 21421818]  [MGI Ref ID J:170449]

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 maintained as a live colony, heterozygotes may be bred. Homozygotes don't breed well.

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* $2085.00
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* $2710.50
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.

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Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.


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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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