Strain Name:

B6.D2-Car2n/J

Stock Number:

001623

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Cryopreserved - Ready for recovery

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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 B6.D2-Car2o    (Changed: 15-DEC-04 )
Type Congenic; Mutant Strain;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Additional information on Congenic nomenclature.
Specieslaboratory mouse
Background Strain C57BL/6J
Donor Strain DBA/2J

Description
In human, CAR2 deficiencies can result in osteopetrosis, renal tubular acidosis, impaired growth, cerebral calcification, and mental retardation. Mice homozygous for Car2<n> do not display cerebral calcification or osteopetrosis, although medial calcification of small arteries has been found in several organs, most notably the male genital tract. The phenotype of these mice includes renal tubular acidosis, doubled urine output, increased urine pH and Cl-, decreased blood pH and HCO-3, phosphatemia, lower plasma bicarbonate, and a smaller body size. Despite smaller body weight, the kidneys are of normal size and plasma potassium and creatinine levels are normal. Type A and B intercalated cells of the kidney are severely depleted. Car2n homozygotes have reduced susceptibility to audiogenic and chemogenic seizures and hippocampal slices from homozygotes are more resistant to hypoxia than are those of wild type controls. Increased CAR4 levels, suggesting a compensation mechanism, have been found in oligodendrocytes and myelinated tracts. Successful liposome-delivered gene therapy has been performed on this mutant. (Lewis et al., 1988; Spicer et al., 1989; Brechue et al., 1991; Tashian, 1992; Velisek et al., 1993A and B, and 1995; Brion et al., 1994 and 1997; Breton et al.1995; Lai et al, 1998.)

Development
DBA/2J males were treated with 200mg/kg N-ethyl-N-nitrosourea then mated to C57BL/6J females10 or more weeks after treatment. Blood and kidney samples from the offspring were assayed by isoelectric focusing and a male was identified that lacked the DBA/2J derived Car2b band. The C57BL/6J derived Car2a band was detected. This mutant male was backcrossed to C57BL/6J. Approximately one quarter of offspring from the mating of these F1 to their mutant father were found to have no Car2 bands in any of multiple tissues assayed. In 1988 this mutation was imported into the laboratory of Dr. Jane Barker at The Jackson Laboratory from Dr. Susan Lewis at Research Triangle Institute. Dr. Barker backcrossed it further onto C57BL/6J and in 1995 C57BL/6J females were bred with homozygous B6.D2-Car2n males, then at N19, and the resulting embryos were cryopreserved. (Lewis et al., 1988; Johnson and Lewis, 1981.)

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).
Osteopetrosis, Autosomal Recessive 3; OPTB3
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.

Car2n/Car2n

        involves: C57BL/6J * DBA/2J
  • renal/urinary system phenotype
  • renal tubular acidosis
    • urine has a more alkaline pH than wild-type when given tap water to drink   (MGI Ref ID J:19268)
  • growth/size/body phenotype
  • postnatal growth retardation
    • smaller than controls starting not later than at 2 weeks of age   (MGI Ref ID J:19268)
  • homeostasis/metabolism phenotype
  • acidosis
    • respiratory acidosis   (MGI Ref ID J:102478)
    • renal tubular acidosis
      • urine has a more alkaline pH than wild-type when given tap water to drink   (MGI Ref ID J:19268)
  • decreased circulating bicarbonate level   (MGI Ref ID J:19268)
  • skeleton phenotype
  • *normal* skeleton phenotype
    • the prominent osteopetrosis found in humans with carbonic anhydrase II deficiency syndrome could not be detected in mice aged up to 15 months   (MGI Ref ID J:19268)
  • digestive/alimentary phenotype
  • abnormal digestive system physiology
    • bicarbonate secretory response of the duodenum to prostaglandin E2 (PGE2) is completely absent in mutants, however basal duodenal bicarbonate secretion is normal   (MGI Ref ID J:102478)
  • abnormal duodenum morphology
    • some mutants exhibit intraepithelial lymphocytes in the duodenum   (MGI Ref ID J:102478)
  • gastric cysts
    • 13% of mutants exhibit gastric cysts   (MGI Ref ID J:102478)
  • stomach epithelial hyperplasia
    • 50% of mutants exhibit mild gastric pit-cell hyperplasia   (MGI Ref ID J:102478)

Car2n/Car2n

        involves: DBA/2J
  • reproductive system phenotype
  • dilated efferent ductules of testis
    • ductules dilated compared to wild-type, with equal or greater volume compared to Esr1-null mice   (MGI Ref ID J:125658)
  • dilated rete testis
    • rete testis dilated compared to wild-type, with equal or greater volume compared to Esr1-null mice   (MGI Ref ID J:125658)
  • reduced male fertility
    • fertility is reduced with aging   (MGI Ref ID J:125658)
  • endocrine/exocrine gland phenotype
  • dilated efferent ductules of testis
    • ductules dilated compared to wild-type, with equal or greater volume compared to Esr1-null mice   (MGI Ref ID J:125658)
  • dilated rete testis
    • rete testis dilated compared to wild-type, with equal or greater volume compared to Esr1-null mice   (MGI Ref ID J:125658)
View Research Applications

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

Car2n related

Cardiovascular Research
Vascular Defects

Cell Biology Research

Developmental Biology Research
Growth Defects

Metabolism Research
Enzyme Deficiency

Neurobiology Research
Epilepsy
      decreased susceptibility to seizures

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Car2n
Allele Name null
Allele Type Chemically induced (ENU)
Common Name(s) CA(II)D; CAII-; Car-20; Car2-; Car2N;
Strain of OriginDBA/2J
Gene Symbol and Name Car2, carbonic anhydrase 2
Chromosome 3
Gene Common Name(s) AI131712; CA II; CA-II; CAC; CAII; Ca2; Car-2; HEL-76; Ltw-5; Lvtw-5; expressed sequence AI131712; liver 20-30 thousand M.Wt protein 5;
Molecular Note The result of ENU mutagenesis, the mutation at the Car2 locus is likely a nonsense or missense mutation. Molecular analysis shows that the mutant gene is not deleted but is transcribed. The CAR2 protein could not be detected by immunodiffusion analysisand Southern analysis indicates no detectable rearrangements or polymorphisms. [MGI Ref ID J:19268]

Genotyping

Genotyping Information

Genotyping Protocols

Car2n-Pyro, Pyrosequencing


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Additional References

Brion LP; Suarez C; Zhang H; Cammer W. 1994. Up-regulation of carbonic anhydrase isozyme IV in CNS myelin of mice genetically deficient in carbonic anhydrase II. J Neurochem 63(1):360-6. [PubMed: 8207439]  [MGI Ref ID J:18790]

Lai LW; Chan DM; Erickson RP; Hsu SJ; Lien YH. 1998. Correction of renal tubular acidosis in carbonic anhydrase II-deficient mice with gene therapy. J Clin Invest 101(7):1320-5. [PubMed: 9525974]  [MGI Ref ID J:46827]

Lewis SE; Erickson RP; Barnett LB; Venta PJ; Tashian RE. 1988. N-ethyl-N-nitrosourea-induced null mutation at the mouse Car-2 locus: an animal model for human carbonic anhydrase II deficiency syndrome. Proc Natl Acad Sci U S A 85(6):1962-6. [PubMed: 3126501]  [MGI Ref ID J:19268]

Car2n related

Breton S; Alper SL; Gluck SL; Sly WS; Barker JE; Brown D. 1995. Depletion of intercalated cells from collecting ducts of carbonic anhydrase II-deficient (CAR2 null) mice. Am J Physiol 269(6 Pt 2):F761-74. [PubMed: 8594870]  [MGI Ref ID J:156006]

Brion LP; Cammer W; Satlin LM; Suarez C; Zavilowitz BJ; Schuster VL. 1997. Expression of carbonic anhydrase IV in carbonic anhydrase II-deficient mice. Am J Physiol 273(2 Pt 2):F234-45. [PubMed: 9277584]  [MGI Ref ID J:42494]

Brion LP; Suarez C; Zhang H; Cammer W. 1994. Up-regulation of carbonic anhydrase isozyme IV in CNS myelin of mice genetically deficient in carbonic anhydrase II. J Neurochem 63(1):360-6. [PubMed: 8207439]  [MGI Ref ID J:18790]

Cammer W. 1998. Glial-cell cultures from brains of carbonic anhydrase II-deficient mutant mice: delay in oligodendrocyte maturation. Neurochem Res 23(3):407-12. [PubMed: 9482254]  [MGI Ref ID J:47049]

Cammer W; Zhang H; Tansey FA. 1995. Effects of carbonic anhydrase II (CAII) deficiency on CNS structure and function in the myelin-deficient CAII-deficient double mutant mouse. J Neurosci Res 40(4):451-7. [PubMed: 7616606]  [MGI Ref ID J:23601]

Goldfarb DS; Sly WS; Waheed A; Charney AN. 2000. Acid-base effects on electrolyte transport in CA II-deficient mouse colon. Am J Physiol Gastrointest Liver Physiol 278(3):G409-15. [PubMed: 10712260]  [MGI Ref ID J:60880]

Gonzalez-Begne M; Nakamoto T; Nguyen HV; Stewart AK; Alper SL; Melvin JE. 2007. Enhanced formation of a HCO3- transport metabolon in exocrine cells of Nhe1-/- mice. J Biol Chem 282(48):35125-32. [PubMed: 17890222]  [MGI Ref ID J:128999]

Hu J; Zhong C; Ding C; Chi Q; Walz A; Mombaerts P; Matsunami H; Luo M. 2007. Detection of near-atmospheric concentrations of CO2 by an olfactory subsystem in the mouse. Science 317(5840):953-7. [PubMed: 17702944]  [MGI Ref ID J:123535]

Kernek KL; Trofatter JA; Mayeda AR; Hofstetter JR. 2004. A locus for circadian period of locomotor activity on mouse proximal chromosome 3. Chronobiol Int 21(3):343-52. [PubMed: 15332441]  [MGI Ref ID J:92583]

Leppilampi M; Parkkila S; Karttunen T; Gut MO; Gros G; Sjoblom M. 2005. Carbonic anhydrase isozyme-II-deficient mice lack the duodenal bicarbonate secretory response to prostaglandin E2. Proc Natl Acad Sci U S A 102(42):15247-52. [PubMed: 16217040]  [MGI Ref ID J:102478]

Lewis SE; Erickson RP; Barnett LB; Venta PJ; Tashian RE. 1988. N-ethyl-N-nitrosourea-induced null mutation at the mouse Car-2 locus: an animal model for human carbonic anhydrase II deficiency syndrome. Proc Natl Acad Sci U S A 85(6):1962-6. [PubMed: 3126501]  [MGI Ref ID J:19268]

Lien YH; Lai LW. 1998. Respiratory acidosis in carbonic anhydrase II-deficient mice. Am J Physiol 274(2 Pt 1):L301-4. [PubMed: 9486217]  [MGI Ref ID J:46053]

Munger SD; Leinders-Zufall T; McDougall LM; Cockerham RE; Schmid A; Wandernoth P; Wennemuth G; Biel M; Zufall F; Kelliher KR. 2010. An olfactory subsystem that detects carbon disulfide and mediates food-related social learning. Curr Biol 20(16):1438-44. [PubMed: 20637621]  [MGI Ref ID J:163768]

Nogradi A; Jonsson N; Walker R; Caddy K; Carter N; Kelly C. 1997. Carbonic anhydrase II and carbonic anhydrase-related protein in the cerebellar cortex of normal and lurcher mice. Brain Res Dev Brain Res 98(1):91-101. [PubMed: 9027408]  [MGI Ref ID J:37700]

Ridderstrale Y; Wistrand PJ. 2000. Membrane-associated carbonic anhydrase activity in the brain of CA II-deficient mice. J Neurocytol 29(4):263-9. [PubMed: 11276178]  [MGI Ref ID J:121401]

Ridderstrale Y; Wistrand PJ; Brechue WF. 1994. Membrane-associated CA activity in the eye of the CA II-deficient mouse. Invest Ophthalmol Vis Sci 35(5):2577-84. [PubMed: 8163345]  [MGI Ref ID J:18513]

Ruusuvuori E; Huebner AK; Kirilkin I; Yukin AY; Blaesse P; Helmy M; Kang HJ; El Muayed M; Hennings JC; Voipio J; Sestan N; Hubner CA; Kaila K. 2013. Neuronal carbonic anhydrase VII provides GABAergic excitatory drive to exacerbate febrile seizures. EMBO J 32(16):2275-86. [PubMed: 23881097]  [MGI Ref ID J:200079]

Savinova OV; Sugiyama F; Martin JE; Tomarev SI; Paigen BJ; Smith RS; John SW. 2001. Intraocular pressure in genetically distinct mice: an update and strain survey. BMC Genet 2(1):12. [PubMed: 11532192]  [MGI Ref ID J:82879]

Simpson JE; Walker NM; Supuran CT; Soleimani M; Clarke LL. 2010. Putative anion transporter-1 (Pat-1, Slc26a6) contributes to intracellular pH regulation during H+-dipeptide transport in duodenal villous epithelium. Am J Physiol Gastrointest Liver Physiol 298(5):G683-91. [PubMed: 20150244]  [MGI Ref ID J:159253]

Singh U; Sun T; Shi W; Schulz R; Nuber UA; Varanou A; Hemberger MC; Elliott RW; Ohta H; Wakayama T; Fundele R. 2005. Expression and functional analysis of genes deregulated in mouse placental overgrowth models: Car2 and Ncam1. Dev Dyn 234(4):1034-45. [PubMed: 16247769]  [MGI Ref ID J:102850]

Sjoblom M; Singh AK; Zheng W; Wang J; Tuo BG; Krabbenhoft A; Riederer B; Gros G; Seidler U. 2009. Duodenal acidity 'sensing' but not epithelial HCO3- supply is critically dependent on carbonic anhydrase II expression. Proc Natl Acad Sci U S A 106(31):13094-9. [PubMed: 19622732]  [MGI Ref ID J:152014]

Stridh MH; Alt MD; Wittmann S; Heidtmann H; Aggarwal M; Riederer B; Seidler U; Wennemuth G; McKenna R; Deitmer JW; Becker HM. 2012. Lactate flux in astrocytes is enhanced by a non-catalytic action of carbonic anhydrase II. J Physiol 590(Pt 10):2333-51. [PubMed: 22451434]  [MGI Ref ID J:197273]

Zhou Q; Clarke L; Nie R; Carnes K; Lai LW; Lien YH; Verkman A; Lubahn D; Fisher JS; Katzenellenbogen BS; Hess RA. 2001. Estrogen action and male fertility: roles of the sodium/hydrogen exchanger-3 and fluid reabsorption in reproductive tract function. Proc Natl Acad Sci U S A 98(24):14132-7. [PubMed: 11698654]  [MGI Ref ID J:125658]

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 & HusbandryCar2n homozygotes are intolerant of NH4Cl in their drinking water. Homozygous females are poor breeders, often producing stillborn pups. Male homozygotes can be used for breeding.

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* $2450.00
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.

Embryos

Price (US dollars $)
Frozen Embryo $1600.00

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 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* $3185.00
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.

Embryos

Price (US dollars $)
Frozen Embryo $2080.00

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 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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