Strain Name:

B6;129S-Dnmt1tm1Jae/J

Stock Number:

002123

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Use Restrictions Apply, see Terms of Use
Mice homozygous for this mutation die at mid-gestation. The embryos are stunted and show a delayed development. DNA from these mice shows a reduction in the level of m5C to about 1/3 that seen in cells from normal wildtype siblings.

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;129S-Dnmttm1Jae    (Changed: 15-DEC-04 )
Type Mutant Stock; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Specieslaboratory mouse
 
Donating InvestigatorDr. Rudolf Jaenisch,   Whitehead Institute (MIT)

Description
Mice homozygous for this mutation die at mid-gestation. The embryos are stunted and show a delayed development. DNA from these mice shows a reduction in the level of m5C to about 1/3 that seen in cells from normal wildtype siblings.

Development
A targeting vector consisting of a neomycin cassette replacement of 900 bp, including the translation start site, was electroporated into J1 ES cells. ES cells were injected into C57BL/6J blastocysts and chimeric male offspring were mated to C57BL/6 females.

Control Information

  Control
   Wild-type from the colony
   101045 B6129SF2/J (approximate)
 
  Considerations for Choosing Controls

Related Strains

Strains carrying   Dnmt1tm1Jae allele
002198   B6.129S4-Dnmt1tm1Jae/J
View Strains carrying   Dnmt1tm1Jae     (1 strain)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI
- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested.
Cerebellar Ataxia, Deafness, and Narcolepsy, Autosomal Dominant; ADCADN   (DNMT1)
Neuropathy, Hereditary Sensory, Type IE; HSN1E   (DNMT1)
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.

Dnmt1tm1Jae/Dnmt1tm1Jae

        involves: 129S4/SvJae
  • mortality/aging
  • complete embryonic lethality
    • die prior to E11   (MGI Ref ID J:1157)
  • embryogenesis phenotype
  • abnormal embryonic tissue morphology
    • 2/3 of embryos show a structure protruding from the lower abdomen   (MGI Ref ID J:1157)
  • embryonic growth arrest
    • embryos fail to develop beyond the stage characteristic of normal E9.5 embryos   (MGI Ref ID J:1157)
  • pale yolk sac
    • yolk sacs lack visible blood or blood vasculature   (MGI Ref ID J:1157)
  • small visceral yolk sac
    • small yolk sac   (MGI Ref ID J:1157)
  • cellular phenotype
  • abnormal DNA methylation
    • total cytosine methylation is about 30% of the level in wild-type   (MGI Ref ID J:1157)
  • abnormal imprinting
    • Ifg2 is not expressed due to altered imprinting   (MGI Ref ID J:110857)
  • decreased cell proliferation
    • fewer mitotic figures in embryos   (MGI Ref ID J:1157)
  • increased apoptosis
    • increase in cell death in embryos   (MGI Ref ID J:1157)
View Research Applications

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

Dnmt1tm1Jae related

Developmental Biology Research
Embryonic Lethality (Homozygous)

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Dnmt1tm1Jae
Allele Name targeted mutation 1, Rudolf Jaenisch
Allele Type Targeted (Hypomorph)
Common Name(s) Dmntn; Dnmt1N; DnmtN; MTase(-); Mtasen;
Mutation Made ByDr. Rudolf Jaenisch,   Whitehead Institute (MIT)
Strain of Origin129S4/SvJae
ES Cell Line NameJ1
ES Cell Line Strain129S4/SvJae
Gene Symbol and Name Dnmt1, DNA methyltransferase (cytosine-5) 1
Chromosome 9
Gene Common Name(s) ADCADN; AIM; CXXC9; DNMT; Dnmt1o; HSN1E; MCMT; MTase; MommeD2; modifier of murine metastable epialleles, D2;
Molecular Note Replacement of 900 bp, including the translation start site, with a neomycin cassette. This is a hypomorphic allele; enzyme activity levels have dropped to approximately 30% of the normal value. [MGI Ref ID J:1157]

Genotyping

Genotyping Information

Genotyping Protocols

Dnmt1tm1Jae, Standard PCR
NEOTD (Generic Neo), Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Li E; Bestor TH; Jaenisch R. 1992. Targeted mutation of the DNA methyltransferase gene results in embryonic lethality. Cell 69(6):915-26. [PubMed: 1606615]  [MGI Ref ID J:1157]

Additional References

Croteau S; Polychronakos C; Naumova AK. 2001. Imprinting defects in mouse embryos: stochastic errors or polymorphic phenotype? Genesis 31(1):11-6. [PubMed: 11668673]  [MGI Ref ID J:71981]

Li E; Beard C; Forster AC; Bestor TH; Jaenisch R. 1993. DNA methylation, genomic imprinting, and mammalian development. Cold Spring Harb Symp Quant Biol 58:297-305. [PubMed: 7956042]  [MGI Ref ID J:20113]

Dnmt1tm1Jae related

Bechtel W; McGoohan S; Zeisberg EM; Muller GA; Kalbacher H; Salant DJ; Muller CA; Kalluri R; Zeisberg M. 2010. Methylation determines fibroblast activation and fibrogenesis in the kidney. Nat Med 16(5):544-50. [PubMed: 20418885]  [MGI Ref ID J:160617]

Berger J; Sansom O; Clarke A; Bird A. 2007. MBD2 is required for correct spatial gene expression in the gut. Mol Cell Biol 27(11):4049-57. [PubMed: 17353267]  [MGI Ref ID J:122224]

Chong S; Vickaryous N; Ashe A; Zamudio N; Youngson N; Hemley S; Stopka T; Skoultchi A; Matthews J; Scott HS; de Kretser D; O'Bryan M; Blewitt M; Whitelaw E. 2007. Modifiers of epigenetic reprogramming show paternal effects in the mouse. Nat Genet 39(5):614-22. [PubMed: 17450140]  [MGI Ref ID J:122400]

Cormier RT; Dove WF. 2000. Dnmt1N/+ reduces the net growth rate and multiplicity of intestinal adenomas in C57BL/6-multiple intestinal neoplasia (Min)/+ mice independently of p53 but demonstrates strong synergy with the modifier of Min 1(AKR) resistance allele. Cancer Res 60(14):3965-70. [PubMed: 10919675]  [MGI Ref ID J:63662]

Eads CA; Nickel AE; Laird PW. 2002. Complete Genetic Suppression of Polyp Formation and Reduction of CpG-Island Hypermethylation in Apc(Min/+) Dnmt1-Hypomorphic Mice. Cancer Res 62(5):1296-9. [PubMed: 11888894]  [MGI Ref ID J:75230]

Ecke I; Petry F; Rosenberger A; Tauber S; Monkemeyer S; Hess I; Dullin C; Kimmina S; Pirngruber J; Johnsen SA; Uhmann A; Nitzki F; Wojnowski L; Schulz-Schaeffer W; Witt O; Hahn H. 2009. Antitumor effects of a combined 5-aza-2'deoxycytidine and valproic acid treatment on rhabdomyosarcoma and medulloblastoma in Ptch mutant mice. Cancer Res 69(3):887-95. [PubMed: 19155313]  [MGI Ref ID J:144974]

Gonzalo S; Jaco I; Fraga MF; Chen T; Li E; Esteller M; Blasco MA. 2006. DNA methyltransferases control telomere length and telomere recombination in mammalian cells. Nat Cell Biol 8(4):416-24. [PubMed: 16565708]  [MGI Ref ID J:129529]

Grandjean V; Yaman R; Cuzin F; Rassoulzadegan M. 2007. Inheritance of an Epigenetic Mark: The CpG DNA Methyltransferase 1 Is Required for De Novo Establishment of a Complex Pattern of Non-CpG Methylation. PLoS ONE 2(11):e1136. [PubMed: 17989773]  [MGI Ref ID J:130349]

Hutnick LK; Huang X; Loo TC; Ma Z; Fan G. 2010. Repression of retrotransposal elements in mouse embryonic stem cells is primarily mediated by a DNA methylation-independent mechanism. J Biol Chem 285(27):21082-91. [PubMed: 20404320]  [MGI Ref ID J:165937]

Jones BK; Levorse JM; Tilghman SM. 1998. Igf2 imprinting does not require its own DNA methylation or H19 RNA. Genes Dev 12(14):2200-7. [PubMed: 9679064]  [MGI Ref ID J:110857]

Kinney SR; Moser MT; Pascual M; Greally JM; Foster BA; Karpf AR. 2010. Opposing roles of Dnmt1 in early- and late-stage murine prostate cancer. Mol Cell Biol 30(17):4159-74. [PubMed: 20584988]  [MGI Ref ID J:163289]

Kutay H; Klepper C; Wang B; Hsu SH; Datta J; Yu L; Zhang X; Majumder S; Motiwala T; Khan N; Belury M; McClain C; Jacob S; Ghoshal K. 2012. Reduced susceptibility of DNA methyltransferase 1 hypomorphic (Dnmt1N/+) mice to hepatic steatosis upon feeding liquid alcohol diet. PLoS One 7(8):e41949. [PubMed: 22905112]  [MGI Ref ID J:189908]

Lei H; Oh SP; Okano M; Juttermann R; Goss KA; Jaenisch R; Li E. 1996. De novo DNA cytosine methyltransferase activities in mouse embryonic stem cells. Development 122(10):3195-205. [PubMed: 8898232]  [MGI Ref ID J:36234]

Li E; Beard C; Jaenisch R. 1993. Role for DNA methylation in genomic imprinting [see comments] Nature 366(6453):362-5. [PubMed: 8247133]  [MGI Ref ID J:16119]

Maatouk DM; Kellam LD; Mann MR; Lei H; Li E; Bartolomei MS; Resnick JL. 2006. DNA methylation is a primary mechanism for silencing postmigratory primordial germ cell genes in both germ cell and somatic cell lineages. Development 133(17):3411-8. [PubMed: 16887828]  [MGI Ref ID J:112224]

Nan X; Hou J; Maclean A; Nasir J; Lafuente MJ; Shu X; Kriaucionis S; Bird A. 2007. Interaction between chromatin proteins MECP2 and ATRX is disrupted by mutations that cause inherited mental retardation. Proc Natl Acad Sci U S A 104(8):2709-14. [PubMed: 17296936]  [MGI Ref ID J:125897]

Oghamian S; Sodir NM; Bashir MU; Shen H; Cullins AE; Carroll CA; Kundu P; Shibata D; Laird PW. 2011. Reduction of pancreatic acinar cell tumor multiplicity in Dnmt1 hypomorphic mice. Carcinogenesis 32(6):829-35. [PubMed: 21362628]  [MGI Ref ID J:172257]

Piccolo FM; Bagci H; Brown KE; Landeira D; Soza-Ried J; Feytout A; Mooijman D; Hajkova P; Leitch HG; Tada T; Kriaucionis S; Dawlaty MM; Jaenisch R; Merkenschlager M; Fisher AG. 2013. Different roles for Tet1 and Tet2 proteins in reprogramming-mediated erasure of imprints induced by EGC fusion. Mol Cell 49(6):1023-33. [PubMed: 23453809]  [MGI Ref ID J:198143]

Roberts AR; Blewitt ME; Youngson NA; Whitelaw E; Chong S. 2011. Reduced dosage of the modifiers of epigenetic reprogramming Dnmt1, Dnmt3L, SmcHD1 and Foxo3a has no detectable effect on mouse telomere length in vivo. Chromosoma 120(4):377-85. [PubMed: 21553025]  [MGI Ref ID J:201510]

Schoeftner S; Blasco MA. 2008. Developmentally regulated transcription of mammalian telomeres by DNA-dependent RNA polymerase II. Nat Cell Biol 10(2):228-36. [PubMed: 18157120]  [MGI Ref ID J:132362]

Shaknovich R; Cerchietti L; Tsikitas L; Kormaksson M; De S; Figueroa ME; Ballon G; Yang SN; Weinhold N; Reimers M; Clozel T; Luttrop K; Ekstrom TJ; Frank J; Vasanthakumar A; Godley LA; Michor F; Elemento O; Melnick A. 2011. DNA methyltransferase 1 and DNA methylation patterning contribute to germinal center B-cell differentiation. Blood 118(13):3559-69. [PubMed: 21828137]  [MGI Ref ID J:177061]

Tanaka M; Puchyr M; Gertsenstein M; Harpal K; Jaenisch R; Rossant J; Nagy A. 1999. Parental origin-specific expression of Mash2 is established at the time of implantation with its imprinting mechanism highly resistant to genome-wide demethylation. Mech Dev 87(1-2):129-42. [PubMed: 10495277]  [MGI Ref ID J:57828]

TeKippe M; Harrison DE; Chen J. 2003. Expansion of hematopoietic stem cell phenotype and activity in Trp53-null mice. Exp Hematol 31(6):521-7. [PubMed: 12829028]  [MGI Ref ID J:115677]

Trasler JM; Trasler DG; Bestor TH; Li E; Ghibu F. 1996. DNA methyltransferase in normal and Dnmtn/Dnmtn mouse embryos. Dev Dyn 206(3):239-47. [PubMed: 8896980]  [MGI Ref ID J:33741]

Trinh BN; Long TI; Nickel AE; Shibata D; Laird PW. 2002. DNA methyltransferase deficiency modifies cancer susceptibility in mice lacking DNA mismatch repair. Mol Cell Biol 22(9):2906-17. [PubMed: 11940649]  [MGI Ref ID J:75745]

Weaver JR; Sarkisian G; Krapp C; Mager J; Mann MR; Bartolomei MS. 2010. Domain-specific response of imprinted genes to reduced DNMT1. Mol Cell Biol 30(16):3916-28. [PubMed: 20547750]  [MGI Ref ID J:162781]

Yung R; Ray D; Eisenbraun JK; Deng C; Attwood J; Eisenbraun MD; Johnson K; Miller RA; Hanash S; Richardson B. 2001. Unexpected effects of a heterozygous dnmt1 null mutation on age-dependent DNA hypomethylation and autoimmunity. J Gerontol A Biol Sci Med Sci 56(6):B268-76. [PubMed: 11382789]  [MGI Ref ID J:69916]

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* $3300.00
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* $4290.00
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
   Wild-type from the colony
   101045 B6129SF2/J (approximate)
 
  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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