Strain Name:

FVB.Cg-Tg(MMTV-vHaras)SH1Led/J

Stock Number:

004363

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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 FVB.Cg-Tg(MMTV-HRAS)1Led/J    (Changed: 15-DEC-04 )
MMTV/v-Ha-ras    (Changed: 15-DEC-04 )
TG.SH    (Changed: 15-DEC-04 )
Type Congenic; Mutant Strain; Transgenic;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Additional information on Congenic nomenclature.
Specieslaboratory mouse
 
Donating InvestigatorDr. Philip Leder,   Harvard Medical School

Description
These transgenic mice express the Harvey RAS (human) gene under the direction of the mouse mammary tumor virus promoter. The majority of expression of the transgene is detected in the mammary tissue and salivary glands. Both male and female transgenic mice develop malignant lymphoid tissue and mammary and salivary gland tumors as early as 5 weeks of age. Half of the female transgenic animals develop tumors by 6 months of age. Histological analysis of mammary tumors revealed most of the tumors were adenocarcinomas and were locally invasive with some cases of metastasis to liver and/or lung. The tumors were found to express the transgene transcript. Protein-tyrosine phosphatase epsilon mRNA and protein was found to be highly expressed only in mammary tumors. In 20% of the transgenic mice diffuse benign hyperplasia develops in the Harderian lacrimal gland causing bilateral exophthalmia. The donating investigator reports hemizygous females develop tumors by delivery of their first litter (i.e. tumorigenesis is accelerated by pregnancy); and hemizygous males develop large salivary gland tumors in the neck and eye opacity by 5 to 6 months of age. The donating investigator has found hemizygous males to have low sperm counts and high incidences of sperm abnormalities resulting in low fertility. This transgenic mouse strain represents a model that may be useful in studies of mammary carcinoma.

Development
A transgenic construct, pA9 chimeric plasmid, containing the p21 structural gene of Harvey murine sarcoma virus (Ha-MuSV) and the MMTV promoter was injected into fertilized B6;CD-1 mouse eggs. Transgenic mice were later backcrossed to FVB/N. The Donating Investigator reports that the mice were backcrossed to FVB/N for at least 10 generations before arriving at The Jackson Laboratory.

Control Information

  Control
   001800 FVB/NJ
 
  Considerations for Choosing Controls

Related Strains

View Strains carrying other alleles of MMTV     (19 strains)

Phenotype

Phenotype Information

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(MMTV-vHaras)SH1Led/Tg(MMTV-vHaras)SH1Led

        involves: 129X1/SvJ * C57BL/6J * CD-1 * FVB
  • tumorigenesis
  • increased carcinoma incidence
    • developed tumors of various sizes that corresponded to moderately to poorly differentiated invasive duct carcinomas with most tumors growing as solid areas that contained no stroma   (MGI Ref ID J:86074)
    • some of the largest tumors were infiltrated by hemorrhage, resulting in a microcystic growth pattern   (MGI Ref ID J:86074)
    • increased mammary adenocarcinoma incidence
      • developed mammary gland tumors between 20 to 45 weeks of age with the mean age for onset at 25 weeks   (MGI Ref ID J:86074)
  • increased metastatic potential
    • 31% developed lung metastases   (MGI Ref ID J:86074)
View Research Applications

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

Cancer Research
Genes Regulating Growth and Proliferation
Increased Tumor Incidence
      Mammary Gland Tumors
Other
      tumor metastasis

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Tg(MMTV-vHaras)SH1Led
Allele Name transgene insertion SH1, Philip Leder
Allele Type Transgenic (Inserted expressed sequence)
Common Name(s) MMTV-H-Ras; MMTV-H-RasG12D; MMTV-v-Ha-ras; MMTV/v-Ha-ras; TG.SH; Tg(MMTV-HRAS)1Led;
Mutation Made ByDr. Philip Leder,   Harvard Medical School
Strain of Origin(CD-1 x C57BL/6J)F1
Expressed Gene vHa-ras, Harvey rat sarcoma viral oncogene homolog,
Promoter MMTV, Mouse Mammary Tumor Virus, MMTV
General Note Multiple transgenic lines were produced.

Both male and female transgenic mice develop malignant lymphoid tissue and mammary and salivary gland tumors as early as 5 weeks of age. Half of the female transgenic animals develop tumors by 6 months of age. Histological analysis of mammary tumors revealed most of the tumors were adenocarcinomas and were locally invasive with some cases of metastasis to liver and/or lung. The tumors were found to express the transgene transcript. Protein-tyrosine phosphatase epsilon mRNA and protein was found to be highly expressed only in mammary tumors. In 20% of the transgenic mice diffuse benign hyperplasia develops in the Harderian lacrimal gland causing bilateral exophthalmia. Hemizygous transgenic female mice develop tumors by delivery time of first litter with tumorigenesis accelerated by pregnancy. Hemizygous transgenic male mice develop large salivary gland tumors in the neck and eye opacity by 5 to 6 months of age. Hemizygous males have low sperm counts and high incidence of sperm abnormalities resulting in low fertility.

Molecular Note This transgene contains the MMTV (mouse mammary tumor virus) promoter and an allele of the Harvey rat sarcoma viral oncogene (viral) carrying two activating point mutations: one in codon 12, Gly12Arg, and one in codon 59, Ala59Thr. The transgenic construct was reported to be highly expressed in the mammary glands and salivary glands, expressed in the Harderian glands, thymus and spleen, slightly expressed in the lungs, ovaries and kidneys, and little or no expression was reported to have been observed inthe liver and skeletal muscle of these mice. [MGI Ref ID J:45456] [MGI Ref ID J:46454] [MGI Ref ID J:90327]
 
 

Genotyping

Genotyping Information

Genotyping Protocols

Tg(MMTV-vHaras)SH1Led, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Sinn E; Muller W; Pattengale P; Tepler I; Wallace R; Leder P. 1987. Coexpression of MMTV/v-Ha-ras and MMTV/c-myc genes in transgenic mice: synergistic action of oncogenes in vivo. Cell 49(4):465-75. [PubMed: 3032456]  [MGI Ref ID J:46454]

Additional References

Elson A; Leder P. 1995. Protein-tyrosine phosphatase epsilon. An isoform specifically expressed in mouse mammary tumors initiated by v-Ha-ras OR neu. J Biol Chem 270(44):26116-22. [PubMed: 7592814]  [MGI Ref ID J:29711]

Tg(MMTV-vHaras)SH1Led related

Adnane J; Jackson RJ; Nicosia SV; Cantor AB; Pledger WJ; Sebti SM. 2000. Loss of p21WAF1/CIP1 accelerates Ras oncogenesis in a transgenic/knockout mammary cancer model Oncogene 19(47):5338-47. [PubMed: 11103935]  [MGI Ref ID J:66183]

Andarawewa KL; Boulay A; Masson R; Mathelin C; Stoll I; Tomasetto C; Chenard MP; Gintz M; Bellocq JP; Rio MC. 2003. Dual stromelysin-3 function during natural mouse mammary tumor virus-ras tumor progression. Cancer Res 63(18):5844-9. [PubMed: 14522908]  [MGI Ref ID J:86074]

Blackshear PE; Goldsworthy SM; Foley JF; McAllister KA; Bennett LM; Collins NK; Bunch DO; Brown P; Wiseman RW; Davis BJ. 1998. Brca1 and Brca2 expression patterns in mitotic and meiotic cells of mice. Oncogene 16(1):61-8. [PubMed: 9467943]  [MGI Ref ID J:45456]

Bulavin DV; Phillips C; Nannenga B; Timofeev O; Donehower LA; Anderson CW; Appella E; Fornace AJ Jr. 2004. Inactivation of the Wip1 phosphatase inhibits mammary tumorigenesis through p38 MAPK-mediated activation of the p16(Ink4a)-p19(Arf) pathway. Nat Genet 36(4):343-50. [PubMed: 14991053]  [MGI Ref ID J:121570]

Cao J; Schulte J; Knight A; Leslie NR; Zagozdzon A; Bronson R; Manevich Y; Beeson C; Neumann CA. 2009. Prdx1 inhibits tumorigenesis via regulating PTEN/AKT activity. EMBO J 28(10):1505-17. [PubMed: 19369943]  [MGI Ref ID J:148785]

Cao Y; Luo JL; Karin M. 2007. IkappaB kinase alpha kinase activity is required for self-renewal of ErbB2/Her2-transformed mammary tumor-initiating cells. Proc Natl Acad Sci U S A 104(40):15852-7. [PubMed: 17890319]  [MGI Ref ID J:125555]

Cardiff RD; Sinn E; Muller W; Leder P. 1991. Transgenic oncogene mice. Tumor phenotype predicts genotype. Am J Pathol 139(3):495-501. [PubMed: 1887859]  [MGI Ref ID J:72086]

Dubernard G; Oster M; Chareyre F; Antoine M; Rouzier R; Uzan S; Aractingi S; Khosrotehrani K. 2009. Increased fetal cell microchimerism in high grade breast carcinomas occurring during pregnancy. Int J Cancer 124(5):1054-9. [PubMed: 19065666]  [MGI Ref ID J:146066]

Elangovan S; Pathania R; Ramachandran S; Ananth S; Padia RN; Srinivas SR; Babu E; Hawthorn L; Schoenlein PV; Boettger T; Smith SB; Prasad PD; Ganapathy V; Thangaraju M. 2013. Molecular mechanism of SLC5A8 inactivation in breast cancer. Mol Cell Biol 33(19):3920-35. [PubMed: 23918800]  [MGI Ref ID J:205014]

Elson A; Leder P. 1995. Protein-tyrosine phosphatase epsilon. An isoform specifically expressed in mouse mammary tumors initiated by v-Ha-ras OR neu. J Biol Chem 270(44):26116-22. [PubMed: 7592814]  [MGI Ref ID J:29711]

Fantozzi A; Christofori G. 2006. Mouse models of breast cancer metastasis. Breast Cancer Res 8(4):212. [PubMed: 16887003]  [MGI Ref ID J:116013]

Feng F; Rittling SR. 2000. Mammary tumor development in MMTV-c-myc/MMTV-v-Ha-ras transgenic mice is unaffected by osteopontin deficiency. Breast Cancer Res Treat 63(1):71-9. [PubMed: 11079161]  [MGI Ref ID J:66199]

Huang AL; Ostrowski MC; Berard D; Hager GL. 1981. Glucocorticoid regulation of the Ha-MuSV p21 gene conferred by sequences from mouse mammary tumor virus. Cell 27(2 Pt 1):245-55. [PubMed: 6277498]  [MGI Ref ID J:90327]

Hundley JE; Koester SK; Troyer DA; Hilsenbeck SG; Subler MA; Windle JJ. 1997. Increased tumor proliferation and genomic instability without decreased apoptosis in MMTV-ras mice deficient in p53. Mol Cell Biol 17(2):723-31. [PubMed: 9001226]  [MGI Ref ID J:37670]

Jackson RJ; Adnane J; Coppola D; Cantor A; Sebti SM; Pledger WJ. 2002. Loss of the cell cycle inhibitors p21(Cip1) and p27(Kip1) enhances tumorigenesis in knockout mouse models. Oncogene 21(55):8486-97. [PubMed: 12466968]  [MGI Ref ID J:80271]

Kiaris H; Politi K; Grimm LM; Szabolcs M; Fisher P; Efstratiadis A; Artavanis-Tsakonas S. 2004. Modulation of notch signaling elicits signature tumors and inhibits hras1-induced oncogenesis in the mouse mammary epithelium. Am J Pathol 165(2):695-705. [PubMed: 15277242]  [MGI Ref ID J:91518]

Kuang SQ; Liao L; Zhang H; Lee AV; O'Malley BW; Xu J. 2004. AIB1/SRC-3 deficiency affects insulin-like growth factor I signaling pathway and suppresses v-Ha-ras-induced breast cancer initiation and progression in mice. Cancer Res 64(5):1875-85. [PubMed: 14996752]  [MGI Ref ID J:88789]

Li Y; Welm B; Podsypanina K; Huang S; Chamorro M; Zhang X; Rowlands T; Egeblad M; Cowin P; Werb Z; Tan LK; Rosen JM; Varmus HE. 2003. Evidence that transgenes encoding components of the Wnt signaling pathway preferentially induce mammary cancers from progenitor cells. Proc Natl Acad Sci U S A 100(26):15853-8. [PubMed: 14668450]  [MGI Ref ID J:87520]

Niederreither K; Harbers M; Chambon P; Dolle P. 1998. Expression of T:G mismatch-specific thymidine-DNA glycosylase and DNA methyl transferase genes during development and tumorigenesis. Oncogene 17(12):1577-85. [PubMed: 9794235]  [MGI Ref ID J:50138]

Radany EH; Hong K; Kesharvarzi S; Lander ES; Bishop JM. 1997. Mouse mammary tumor virus/v-Ha-ras transgene-induced mammary tumors exhibit strain-specific allelic loss on mouse chromosome 4. Proc Natl Acad Sci U S A 94(16):8664-9. [PubMed: 9238034]  [MGI Ref ID J:42251]

Ray D; Terao Y; Fuhrken PG; Ma ZQ; DeMayo FJ; Christov K; Heerema NA; Franks R; Tsai SY; Papoutsakis ET; Kiyokawa H. 2007. Deregulated CDC25A expression promotes mammary tumorigenesis with genomic instability. Cancer Res 67(3):984-91. [PubMed: 17283130]  [MGI Ref ID J:118218]

Ray D; Terao Y; Nimbalkar D; Hirai H; Osmundson EC; Zou X; Franks R; Christov K; Kiyokawa H. 2007. Hemizygous disruption of Cdc25A inhibits cellular transformation and mammary tumorigenesis in mice. Cancer Res 67(14):6605-11. [PubMed: 17638870]  [MGI Ref ID J:123144]

Sun J; Ohkanda J; Coppola D; Yin H; Kothare M; Busciglio B; Hamilton AD; Sebti SM. 2003. Geranylgeranyltransferase I inhibitor GGTI-2154 induces breast carcinoma apoptosis and tumor regression in H-Ras transgenic mice. Cancer Res 63(24):8922-9. [PubMed: 14695209]  [MGI Ref ID J:87068]

Sypniewska RK; Hoflack L; Bearss DJ; Gravekamp C. 2002. Potential mouse tumor model for pre-clinical testing of mage-specific breast cancer vaccines. Breast Cancer Res Treat 74(3):221-33. [PubMed: 12211215]  [MGI Ref ID J:79084]

Tront JS; Hoffman B; Liebermann DA. 2006. Gadd45a Suppresses Ras-Driven Mammary Tumorigenesis by Activation of c-Jun NH2-Terminal Kinase and p38 Stress Signaling Resulting in Apoptosis and Senescence. Cancer Res 66(17):8448-54. [PubMed: 16951155]  [MGI Ref ID J:112408]

Wulf G; Garg P; Liou YC; Iglehart D; Lu KP. 2004. Modeling breast cancer in vivo and ex vivo reveals an essential role of Pin1 in tumorigenesis. EMBO J 23(16):3397-407. [PubMed: 15257284]  [MGI Ref ID J:92164]

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 & HusbandryThis is a very difficult line to breed. Hemizygous females typically produce only one to two litters due to complications in lactation and only 10% of males are reported fertile. The Jackson Laboratory maintains this line by transplanting the ovaries of hemizygous females into compatible hosts. We also recommend that all hemizygous males be used for mating to help supplement breeding. Males that fail to breed after 60 days are generally considered nonproductive.

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
   001800 FVB/NJ
 
  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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"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCTS" means biological materials supplied by JACKSON, and their derivatives. "RECIPIENT" means each recipient of MICE, PRODUCTS, or services provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than the internal research, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services. Acceptance of MICE or PRODUCTS from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON's prior written authorization.

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