Strain Name:

B6.C-Tg(Ins2-GP)34-20Olds/MvhJ

Stock Number:

005500

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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; Transgenic;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Additional information on Congenic nomenclature.
Mating System+/+ sibling x Hemizygote         (Female x Male)   24-APR-08
Specieslaboratory mouse
Background Strain C57BL/6J
Donor Strain (C57BL/6 x BALB)F2
H2 Haplotypeb
GenerationN16F?N17p (09-NOV-05)
Generation Definitions
 
Donating InvestigatorDr. Matthais von Herrath,   La Jolla Institute for Allergy and Immun

Appearance
black
Related Genotype: a/a

Description
Transgenic mice were created with the Lymphocytic choriomeningitis virus (LCMV) glycoprotein(GP) or nucleoprotein (NP) under the control of the rat insulin promoter. Ins2-GP expression was determined only in the pancreas by RT-PCR (von Herrath et al 1994). Tg(Ins2-GP)34-20Olds untreated mice rarely develop insulin-dependent diabetes mellitus (IDDM). When challenged with LCMV they develop IDDM. The B6.C -Tg(Ins2-GP)34-20Olds mice (H2b) exhibit a rapid (10-14 days) onset of IDDM compared to C.B6-Tg(Ins2-NP)25-3Olds mice (H2d) (10-21 days) or B6.C -Tg(Ins2-NP)25-3Olds mice (H2b) (30-120 days) (Oldstone et al.,1991; von Herrath et al.,1994). Thymic expression of nucleoprotein has been shown to be responsible for this delayed onset of IDDM. Thymi from newborn B6.C -Tg(Ins2-GP)34-20Olds transplanted into nude hosts produce a primary CTL response when challenged with LCMV. CD8 T cells are required for IDDM development in both glycoprotein and nucleoprotein transgenic mice, as is interferon gamma. In interferon gamma deficient transgenics stimulated with LCMV, CTLs were present in the pancreas and around the islets of Langerhans, but did not infiltrate the islets. Additionally, nucleoprotein transgenic animals require the presence of CD4 T cells. (von Herrath, et al, 1994 and 1997)

A singledose injection of anti CD80, anti CD86 or anti CD80/anti CD86 antibodies does not prevent LCMV induced diabetes in either the GP or NP transgenic mice. LCMV challenged GP transgenic mice are partially protected from diabetes by anti CD80 antibodies and completely protected by anti CD86 or anti CD80/CD86 antibodies injected daily for 14 days. However, LCMV challenged NP transgenic mice have accelerated diabetes onset when treated with anti CD80/CD86 antibodies injected daily for 14 days. LCMV induced diabetes is prevented in NP and GP transgenic mice treated with anti TNFRSF5 when treated within a defined time window. Splenocytes from these protected mice adoptively transferred disease resistance to LCMV- challenged pre diabetic GP transgenic mice. The cells thatconfer protection express ITGAX5, NK1.1 and DX5. The spleens of anti TNFRSF5 protected mice have an increased population of ITGAX5 expressing cells. When this population of cells is further fractionated into ITGAX5+, DX5+ cells, the recipient mice acquire protection from diabetes. (Homann et al., 2002)

Development
B6.C-Tg(Ins2-GP)34-20Olds/MvhJ expresses the lymphocytic choriomeningitis virus (LCMV) glycoprotein (GP) under control of the rat insulin promoter, (Ins2, commonly designated RIP). The transgene was first inserted by Oldstone, et al (1991) into C57BL/6 (H2b) x Balb/WEHI (H2d) F2 oocytes. Line 34-20, maintained by Herrath et al., (1994, 2000) has been backcrossed to C57BL/6 (H2b) for at least 10 generations. In 2005 this strain arrived at The Jackson Laboratory and is maintained Tg/? x Tg/?.

Control Information

  Control
   Noncarrier
   000664 C57BL/6J
 
  Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Ins2
005534   B10.Cg-H2d Tg(Ins2-HA)165Bri/ShrmJ
005715   B6.Cg H2g7-Tg(Ins2-CD80)3B7Flv/LwnJ
004826   B6.Cg-Tg(Ins2-NP)25-3Olds/MhvJ
003573   B6.Cg-Tg(Ins2-cre)25Mgn/J
018960   B6N.Cg-Tg(Ins2-cre)25Mgn/J
005713   C.Cg-Tg(Ins2-CD80)3B7Flv/LwnJ
005533   C.Cg-Tg(Ins2-HA)165Bri/ShrmJ
004827   C.Cg-Tg(Ins2-NP)25-3Olds/MvhJ
005432   C57BL/6-Tg(Ins2-OVA)307Wehi/WehiJ
005433   C57BL/6-Tg(Ins2-OVA)59Wehi/WehiJ
005431   C57BL/6-Tg(Ins2-TFRC/OVA)296Wehi/WehiJ
005564   FVB(Cg)-Tg(Ins2-CALM1)26Ove Tg(Cryaa-TAg)1Ove/PneJ
008232   FVB/N-Tg(Ins2-IAPP)RHFSoel/J
005522   NOD-Tg(Ins2*Y16A)1Ell/GseJ
005523   NOD-Tg(Ins2*Y16A)3Ell/GseJ
003499   NOD-Tg(Ins2-Fasl)24Ach
004346   NOD.Cg-Prkdcscid Tg(Ins2-CD80)3B7Flv/DvsJ
004230   NOD.Cg-Prkdcscid Tg(Ins2-E3)1Dvs/DvsJ
003843   NOD.Cg-Prkdcscid Tg(Ins2-GAD2)1Lt/LtJ
003844   NOD.Cg-Prkdcscid Tg(Ins2-GAD2)2Lt/LtJ
007840   NOD.Cg-Prkdcscid Tg(Ins2-CD86)12B70Flv/FswJ
005524   NOD.Cg-Tg(Ins2*Y16A)1Ell Ins1tm1Jja Ins2tm1Jja/GseJ
005525   NOD.Cg-Tg(Ins2*Y16A)3Ell Ins1tm1Jja Ins2tm1Jja/GseJ
006254   NOD.Cg-Tg(Ins2-Ccl21b)2Cys/JbsJ
006154   NOD.Cg-Tg(Ins2-Cxcl13)1Cys/JbsJ
003869   NOD.Cg-Tg(Ins2-E3)1Dvs/DvsJ
005685   NOD.Cg-Tg(Ins2-HA)165Bri/ShrmJ
002380   NOD.Cg-Tg(Ins2-TAg)1Lt Prkdcscid/DvsJ
023972   NOD.Cg-Tg(Ins2-cre/ERT)1Dam/SbwJ
004602   NOD.Cg-Tg(Ins2-rtTA)2Doi/DoiJ
004937   NOD.Cg-Tg(Ins2-tTA)1Doi/DoiJ
005734   NOD/Lt-Tg(Ins2-rtTA)1Ach/AchJ
005870   NOD/ShiLt(Cg)-Tg(Ins2-GAD2)2Lt/J
006777   NOD/ShiLt-Tg(Ins2-Cd274)2Mdos/MdosJ
005733   NOD/ShiLt-Tg(Ins2-Fas*I246N)1Ach/AchJ
003074   NOD/ShiLt-Tg(Ins2-GAD2)1Lt/LtJ
002033   NOD/ShiLt-Tg(Ins2-TAg)1Lt/J
004986   NOD/ShiLt-Tg(Ins2-cre)3Lt/LtJ
003855   NOD/ShiLt-Tg(Ins2-cre)5Lt/LtJ
004987   NOD/ShiLt-Tg(Ins2-cre)6Lt/LtJ
004226   NOD/ShiLtDvs-Tg(Ins2-E3*309)5Dvs/DvsJ
004227   NOD/ShiLtDvs-Tg(Ins2-E3*704)2Dvs/DvsJ
004968   NOD/ShiLtDvs-Tg(Ins2-E3*734)3Dvs/DvsJ
004990   NOD/ShiLtDvs-Tg(Ins2-E3*734)4Dvs/DvsJ
005714   NOR.Cg-Tg(Ins2-CD80)3B7Flv/LwnJ
008122   STOCK Tg(Ins2-cre/ERT)1Dam/J
008755   STOCK Tg(Ins2-rtTA)2Efr Tg(teto-DTA)1Gfi/J
008250   STOCK Tg(Ins2-rtTA)2Efr/J
View Strains carrying other alleles of Ins2     (48 strains)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI
- Characteristics of this human disease are associated with transgenes and other mutation types in the mouse.
Diabetes Mellitus, Insulin-Dependent; IDDM
View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

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

Tg(Ins2-GP)34-20Olds/0

        involves: BALB/c * C57BL/6
  • homeostasis/metabolism phenotype
  • decreased circulating insulin level
    • hypoinsulinemia is exhibited by transgenic mice accompanying increased glucose levels and islet infiltration   (MGI Ref ID J:81287)
  • increased circulating glucose level
    • mice are considered diabetic after a blood glucose measure of >300 mg/dl   (MGI Ref ID J:81287)
  • immune system phenotype
  • abnormal lymphocyte physiology
    • on a B6 background, transgenic mice cannot exhibit a primary CTL response   (MGI Ref ID J:81287)
    • abnormal T cell physiology
      • depletion of CD8+ lymphocytes with a monoclonal antibody inhibited development of diabetes   (MGI Ref ID J:81287)
  • increased susceptibility to autoimmune diabetes
    • mice rapidly develop diabetes (glucose levels >300 mg/dl) 10-14 days after viral (LCMV) challenge   (MGI Ref ID J:81287)
  • endocrine/exocrine gland phenotype
  • abnormal pancreatic islet morphology
    • mononuclear cells infiltrate the islets of transgenic mice 5-10 days after viral innoculation   (MGI Ref ID J:81287)
    • absent pancreatic beta cells
      • no beta cells are detected at 14 days after LCMV infection   (MGI Ref ID J:81287)
  • hematopoietic system phenotype
  • abnormal lymphocyte physiology
    • on a B6 background, transgenic mice cannot exhibit a primary CTL response   (MGI Ref ID J:81287)
    • abnormal T cell physiology
      • depletion of CD8+ lymphocytes with a monoclonal antibody inhibited development of diabetes   (MGI Ref ID J:81287)
View Research Applications

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

Diabetes and Obesity Research
Type 1 Diabetes (IDDM)

Immunology, Inflammation and Autoimmunity Research
Autoimmunity
      Type 1 Diabetes

Research Tools
Diabetes and Obesity Research

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Tg(Ins2-GP)34-20Olds
Allele Name transgene insertion 34-20, Michael BA Oldstone, MD
Allele Type Transgenic (Inserted expressed sequence)
Common Name(s) LCMV GP; RIP GP H2b; RIP GP34-20; RIP-GP34-20; RIP-LCMV GP;
Mutation Made ByDr. Michael Oldstone,   The Scripps Research Institute
Strain of Origin(C57BL/6 x BALB/Wehi)F2
Expressed Gene LCMV-GP, lymphocytic choriomeningitis virus glycoprotein,
Promoter Ins2, insulin 2, rat
Molecular Note This transgene encodes the glycoprotein (GP) from Armstrong's clone of the lymphocytic choriomeningitis virus (LCMV) regulated by the rat insulin promoter. Upstream of the GP cDNA are 660 base pairs of regulatory elements in addition to the rat insulin promoter. Downstream of the GP c-DNA is the SV40 small T-antigen intron and late polyadenylation signal. RT-PCR analysis demonstrated that the transcript was expressed in the pancreas but not the thymus, spleen, liver, kidney, heart, muscle or lung. [MGI Ref ID J:81287]
 
 

Genotyping

Genotyping Information

Genotyping Protocols

Tg(Ins2-GP)34-20Olds, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Additional References

Tg(Ins2-GP)34-20Olds related

Bresson D; von Herrath MG. 2011. Anti-thymoglobulin (ATG) treatment does not reverse type 1 diabetes in the acute virally induced rat insulin promoter-lymphocytic choriomeningitis virus (RIP-LCMV) model. Clin Exp Immunol 163(3):375-80. [PubMed: 21235534]  [MGI Ref ID J:169310]

Christen S; Coppieters K; Rose K; Holdener M; Bayer M; Pfeilschifter JM; Hintermann E; von Herrath MG; Aurrand-Lions M; Imhof BA; Christen U. 2013. Blockade but not overexpression of the junctional adhesion molecule C influences virus-induced type 1 diabetes in mice. PLoS One 8(1):e54675. [PubMed: 23372751]  [MGI Ref ID J:195794]

Filippi CM; Juedes AE; Oldham JE; Ling E; Togher L; Peng Y; Flavell RA; von Herrath MG. 2008. Transforming growth factor-beta suppresses the activation of CD8+ T-cells when naive but promotes their survival and function once antigen experienced: a two-faced impact on autoimmunity. Diabetes 57(10):2684-92. [PubMed: 18689691]  [MGI Ref ID J:142144]

Hall HT; Wilhelm MT; Saibil SD; Mak TW; Flavell RA; Ohashi PS. 2008. RIP2 contributes to Nod signaling but is not essential for T cell proliferation, T helper differentiation or TLR responses. Eur J Immunol 38(1):64-72. [PubMed: 18085666]  [MGI Ref ID J:130818]

Holz A; Bot A; Coon B; Wolfe T; Grusby MJ; von Herrath MG. 1999. Disruption of the STAT4 signaling pathway protects from autoimmune diabetes while retaining antiviral immune competence. J Immunol 163(10):5374-82. [PubMed: 10553062]  [MGI Ref ID J:107047]

Holz A; Brett K; Oldstone MB. 2001. Constitutive beta cell expression of IL-12 does not perturb self-tolerance but intensifies established autoimmune diabetes. J Clin Invest 108(12):1749-58. [PubMed: 11748258]  [MGI Ref ID J:134571]

Homann D; Holz A; Bot A; Coon B; Wolfe T; Petersen J; Dyrberg TP; Grusby MJ; von Herrath MG. 1999. Autoreactive CD4+ T cells protect from autoimmune diabetes via bystander suppression using the IL-4/Stat6 pathway. Immunity 11(4):463-72. [PubMed: 10549628]  [MGI Ref ID J:96857]

Homann D; Jahreis A; Wolfe T; Hughes A; Coon B; van Stipdonk MJ; Prilliman KR; Schoenberger SP; von Herrath MG. 2002. CD40L blockade prevents autoimmune diabetes by induction of bitypic NK/DC regulatory cells. Immunity 16(3):403-15. [PubMed: 11911825]  [MGI Ref ID J:96858]

Juedes AE; Rodrigo E; Togher L; Glimcher LH; von Herrath MG. 2004. T-bet controls autoaggressive CD8 lymphocyte responses in type 1 diabetes. J Exp Med 199(8):1153-62. [PubMed: 15096540]  [MGI Ref ID J:121024]

Lang PA; Cervantes-Barragan L; Verschoor A; Navarini AA; Recher M; Pellegrini M; Flatz L; Bergthaler A; Honda K; Ludewig B; Ohashi PS; Lang KS. 2009. Hematopoietic cell-derived interferon controls viral replication and virus-induced disease. Blood 113(5):1045-52. [PubMed: 18971424]  [MGI Ref ID J:145035]

Martinic MM; Juedes AE; Bresson D; Homann D; Skak K; Huber C; Ling E; Ejrnaes M; Wolfe T; Togher L; Christen U; von Herrath MG. 2007. Minimal impact of a de novo-expressed beta-cell autoantigen on spontaneous diabetes development in NOD mice. Diabetes 56(4):1059-68. [PubMed: 17395746]  [MGI Ref ID J:122080]

Muchamuel T; Basler M; Aujay MA; Suzuki E; Kalim KW; Lauer C; Sylvain C; Ring ER; Shields J; Jiang J; Shwonek P; Parlati F; Demo SD; Bennett MK; Kirk CJ; Groettrup M. 2009. A selective inhibitor of the immunoproteasome subunit LMP7 blocks cytokine production and attenuates progression of experimental arthritis. Nat Med 15(7):781-7. [PubMed: 19525961]  [MGI Ref ID J:151526]

Oldstone MB; Edelmann KH; McGavern DB; Cruite JT; Welch MJ. 2012. Molecular anatomy and number of antigen specific CD8 T cells required to cause type 1 diabetes. PLoS Pathog 8(11):e1003044. [PubMed: 23209415]  [MGI Ref ID J:195572]

Rhode A; Pauza ME; Barral AM; Rodrigo E; Oldstone MB; von Herrath MG; Christen U. 2005. Islet-specific expression of CXCL10 causes spontaneous islet infiltration and accelerates diabetes development. J Immunol 175(6):3516-24. [PubMed: 16148094]  [MGI Ref ID J:116715]

Van Belle TL; Esplugues E; Liao J; Juntti T; Flavell RA; von Herrath MG. 2011. Development of autoimmune diabetes in the absence of detectable IL-17A in a CD8-driven virally induced model. J Immunol 187(6):2915-22. [PubMed: 21832162]  [MGI Ref ID J:179258]

von Herrath MG; Dockter J; Oldstone MB. 1994. How virus induces a rapid or slow onset insulin-dependent diabetes mellitus in a transgenic model. Immunity 1(3):231-42. [PubMed: 7889411]  [MGI Ref ID J:81287]

von Herrath MG; Oldstone MB. 1997. Interferon-gamma is essential for destruction of beta cells and development of insulin-dependent diabetes mellitus. J Exp Med 185(3):531-9. [PubMed: 9053453]  [MGI Ref ID J:96856]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

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

Colony Maintenance

Mating System+/+ sibling x Hemizygote         (Female x Male)   24-APR-08
Diet Information LabDiet® 5K52/5K67

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.

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 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.

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 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.

General Supply Notes

Control Information

  Control
   Noncarrier
   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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