Strain Name:

B6.Cg-Tg(Pax8-rtTA2S*M2)1Koes/J

Stock Number:

007176

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Availability:

Cryopreserved - Ready for recovery

Use Restrictions Apply, see Terms of Use
These Pax8-rtTA mice provide a Tet-On tool that allows the inducible expression of genes in renal tubular epithelial cells, and may be useful in studying renal disorders such as fibrosis or polycystic kidney disease, renal cancer, and Tuberous Sclerosis (along with Stock No. 005680).

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.
Specieslaboratory mouse
GenerationN5pN1
Generation Definitions
 
Donating Investigator IMR Colony,   The Jackson Laboratory

Description
Transgenic Pax8-rtTA mice are viable and fertile. These mice express an optimized reverse tetracycline-controlled transactivator (rtTA2S-M2) protein under the control of the murine Pax8 promoter, which directs expression to proximal and distal tubules and the collecting duct system of both embryonic and adult kidney. The rtTA2S-M2 variant of rtTA contains five amino acid changes in the TetR moiety (S12G, E19G, A56P, D148E, and H179R) and a synthetic optimized transactivating domain, resulting in reduced basal activity and enhanced doxycycline sensitivity compared to wild-type rtTA. When mated to a second strain carrying a gene of interest under the regulatory control of a tetracycline-responsive promoter element (TRE or tetO), expression of the target gene in kidney cells is induced with administration of the tetracycline analog, doxycycline (dox). These Pax8-rtTA mice provide a Tet-On tool that allows the inducible expression of genes in renal tubular epithelial cells, and may be useful in studying renal disorders such as fibrosis or polycystic kidney disease, renal cancer, and Tuberous Sclerosis.

In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.

Development
The Pax8-rtTA construct was designed to contain an optimized rtTA variant (rtTA2s-M2) cDNA and SV40 polyA sequence replaced at the endogenous ATG translational start site of a murine Pax8 sequence. This 6.6 kb transgene was microinjected into the pronucleus of one-cell fertilized mouse embryos obtained from superovulated F2 (C57BL/6 x DBA) females, which were then implanted into pseudopregnant foster mice. Founder mice were bred to C57BL/6 mice, and the resulting transgenic offspring were bred together for many generations prior to arrival at The Jackson Laboratory. Upon arrival, some mice were backcrossed to C57BL/6J for at least 5 generations to generate this congenic strain (Stock No. 007176). The Pax8-rtTA construct integrated approximately five copies in a head-to-tail orientation within a mouse L1 line repetitive element (which are located throughout the genome).

Control Information

  Control
   Noncarrier
   000664 C57BL/6J
 
  Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of rtTA
016567   129S.Cg-Tg(Hoxb7-rtTA*M2)2Cos/J
017983   B6.Cg-Col1a1tm9(tetO-Dnmt3b_i1)Jae Gt(ROSA)26Sortm1(rtTA*M2)Jae/J
014588   B6.Cg-Gt(ROSA)26Sortm1(rtTA*M2)Jae Col1a1tm6(tetO-MSI2)Jae/J
014602   B6.Cg-Gt(ROSA)26Sortm1(rtTA*M2)Jae Col1a1tm1(tetO-mCherry)Eggn/J
023749   B6.Cg-Gt(ROSA)26Sortm1(rtTA*M2)Jae Tg(tetO-Pou5f1,-Sox2,-Klf4,-Myc)1Srn/J
006965   B6.Cg-Gt(ROSA)26Sortm1(rtTA*M2)Jae/J
005670   B6.Cg-Gt(ROSA)26Sortm1(rtTA,EGFP)Nagy/J
016997   B6.Cg-Tg(Axin2-rtTA2S*M2)7Cos/J
012418   B6.Cg-Tg(CD68-rtTA2S*M2)3Mpil/Mmjax
014098   B6.Cg-Tg(GFAP-rtTA*M2)1Rmra/J
006235   B6.Cg-Tg(SFTPC-rtTA)5Jaw/J
006232   B6.Cg-Tg(Scgb1a1-rtTA)1Jaw/J
021025   B6;129-Gt(ROSA)26Sortm1(rtTA*M2)Jae Col1a1tm1(tetO-cre)Haho/J
006911   B6;129-Gt(ROSA)26Sortm1(rtTA*M2)Jae Col1a1tm2(tetO-Pou5f1)Jae/J
016836   B6;129S4-Gt(ROSA)26Sortm1(rtTA*M2)Jae Col1a1tm7(tetO-HIST1H2BJ/GFP)Jae/J
012433   B6;C3-Tg(ACTA1-rtTA,tetO-cre)102Monk/J
021187   B6;FVB-Tg(Pbsn-rtTA*M2)42Xy/J
010574   B6;SJL-Tg(Gh1-rtTA)4-3Jek/J
007678   B6;SJL-Tg(KRT14-rtTA)208Jek/J
010576   B6;SJL-Tg(MMTV-rtTA)4-1Jek/J
010549   B6N.Cg-Tg(Prkcd-glc-1-rtTA)2And/J
016532   B6N.FVB(Cg)-Tg(CAG-rtTA3)4288Slowe/J
006245   C.Cg-Tg(SFTPC-rtTA)5Jaw/J
006242   C.Cg-Tg(Scgb1a1-rtTA)1Jaw/J
017955   C57BL/6-Tg(Gfap-rtTA,tetO-MAOB,-lacZ)1Jkan/J
008099   FVB-Tg(KRT14-rtTA)F42Efu/J
004127   FVB-Tg(Nes-rtTA)306Rvs/J
008326   FVB-Tg(Pomc-rtTA)1Rck/J
006225   FVB.Cg-Tg(SFTPC-rtTA)5Jaw/J
006222   FVB.Cg-Tg(Scgb1a1-rtTA)1Jaw/J
008202   FVB/N-Tg(NPHS2-rtTA2*M2)1Jbk/J
006875   FVB/N-Tg(Tagln-rtTA)E1Jwst/J
004602   NOD.Cg-Tg(Ins2-rtTA)2Doi/DoiJ
005734   NOD/Lt-Tg(Ins2-rtTA)1Ach/AchJ
011004   STOCK Gt(ROSA)26Sortm1(rtTA*M2)Jae Col1a1tm3(tetO-Pou5f1,-Sox2,-Klf4,-Myc)Jae/J
011011   STOCK Gt(ROSA)26Sortm1(rtTA*M2)Jae Col1a1tm4(tetO-Pou5f1,-Sox2,-Klf4,-Myc)Jae/J
011013   STOCK Gt(ROSA)26Sortm1(rtTA*M2)Jae Col1a1tm5(tetO-Pou5f1,-Klf4,-Myc)Jae/J
005572   STOCK Gt(ROSA)26Sortm1(rtTA,EGFP)Nagy/J
016116   STOCK Waptm2(rtTA)Kuw/J
003273   STOCK Tg(CMV-rtTA)4Bjd/J
018156   STOCK Tg(Drd1a-rtTA)ARgmk/J
019110   STOCK Tg(Hoxb7-rtTA*M2)RS40BCos/Mmjax
008755   STOCK Tg(Ins2-rtTA)2Efr Tg(teto-DTA)1Gfi/J
008250   STOCK Tg(Ins2-rtTA)2Efr/J
017519   STOCK Tg(KRT5-rtTA)T2D6Sgkd/J
016146   STOCK Tg(SFTPC-rtTA)2Jaw/J
016145   STOCK Tg(Scgb1a1-rtTA)2Jaw/J
005493   STOCK Tg(Tek-rtTA,TRE-lacZ)1425Tpr/J
View Strains carrying other alleles of rtTA     (48 strains)

Additional Web Information

Tet Expression Systems

Phenotype

Phenotype Information

View Research Applications

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

Developmental Biology Research
Internal/Organ Defects
      kidney

Endocrine Deficiency Research
Kidney Defects

Internal/Organ Research
Kidney Defects
      polycystic kidney disease

Research Tools
Genetics Research
      Tissue/Cell Markers
      Tissue/Cell Markers: kidney specific marker
Tet Expression Systems
      tTA/rtTA Expressing Strains

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Tg(Pax8-rtTA2S*M2)1Koes
Allele Name transgene insertion 1, Robert Koesters
Allele Type Transgenic (Inserted expressed sequence)
Common Name(s) Pax8-rtTA;
Mutation Made By Robert Koesters,   Universitaetsklinikum Heidelberg
Strain of Origin(C57BL/6 x DBA)F2
Site of Expressionexpression is directed to proximal and distal tubules and the collecting duct system of both embryonic and adult kidney.
Expressed Gene rtTA, reverse tetracycline-controlled transactivator, E. coli
The tetracycline repressor gene (Tetr), arose from chemically mutated Escherichia coli genome which was screened for tetracycline dependence (Gossen and Bujard, 1992). One mutant with a four amino acid residue change (rTetR) exhibited dependence on tetracycline for induction of the targeted gene and was used in the rtTA construct (Gossen et al, 1995). rTetr was fused at the C-terminus with the viral co-activator, virion protein 16 of the herpes simplex virus (VP-16).
Promoter Pax8, paired box 8, mouse, laboratory
General Note Phenotypic Similarity to Human Syndrome: adult onset polycystic kidney disease in mice hemizygous for Tg(Pax8-rtTA2S*M2)1Koes and Tg(tetO-MYC)36aBop (J:1409250)
Molecular Note he Pax8-rtTA construct contains an optimized rtTA variant (rtTA2s-M2) cDNA and SV40 polyA sequence replaced at the endogenous ATG translational start site of a murine Pax8 sequence. The rtTA2S*M2 variant contains 5 amino acid changes in the TetR moiety (S12G, E19G, A56P, D148E, and H179R) and a synthetic optimized transactivating domain, resulting in reduced basal activity and enhanced doxycycline sensitivity compared to wild-type rtTA. [MGI Ref ID J:140925]
 
 

Genotyping

Genotyping Information

Genotyping Protocols

Tg(Pax8-rtTA2S*M2)1Koes, Melt Curve Analysis
Tg(Pax8-rtTA2S*M2)1Koes, QPCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Traykova-Brauch M; Schonig K; Greiner O; Miloud T; Jauch A; Bode M; Felsher DW; Glick AB; Kwiatkowski DJ; Bujard H; Horst J; von Knebel Doeberitz M; Niggli FK; Kriz W; Grone HJ; Koesters R. 2008. An efficient and versatile system for acute and chronic modulation of renal tubular function in transgenic mice. Nat Med 14(9):979-84. [PubMed: 18724376]  [MGI Ref ID J:140925]

Additional References

Tg(Pax8-rtTA2S*M2)1Koes related

Faresse N; Lagnaz D; Debonneville A; Ismailji A; Maillard M; Fejes-Toth G; Naray-Fejes-Toth A; Staub O. 2012. Inducible kidney-specific Sgk1 knockout mice show a salt-losing phenotype. Am J Physiol Renal Physiol 302(8):F977-85. [PubMed: 22301619]  [MGI Ref ID J:183421]

Grahammer F; Haenisch N; Steinhardt F; Sander L; Roerden M; Arnold F; Cordts T; Wanner N; Reichardt W; Kerjaschki D; Ruegg MA; Hall MN; Moulin P; Busch H; Boerries M; Walz G; Artunc F; Huber TB. 2014. mTORC1 maintains renal tubular homeostasis and is essential in response to ischemic stress. Proc Natl Acad Sci U S A 111(27):E2817-26. [PubMed: 24958889]  [MGI Ref ID J:212166]

Hakroush S; Moeller MJ; Theilig F; Kaissling B; Sijmonsma TP; Jugold M; Akeson AL; Traykova-Brauch M; Hosser H; Hahnel B; Grone HJ; Koesters R; Kriz W. 2009. Effects of increased renal tubular vascular endothelial growth factor (VEGF) on fibrosis, cyst formation, and glomerular disease. Am J Pathol 175(5):1883-95. [PubMed: 19834063]  [MGI Ref ID J:154686]

Koesters R; Kaissling B; Lehir M; Picard N; Theilig F; Gebhardt R; Glick AB; Hahnel B; Hosser H; Grone HJ; Kriz W. 2010. Tubular overexpression of transforming growth factor-beta1 induces autophagy and fibrosis but not mesenchymal transition of renal epithelial cells. Am J Pathol 177(2):632-43. [PubMed: 20616344]  [MGI Ref ID J:163476]

Lan R; Geng H; Polichnowski AJ; Singha PK; Saikumar P; McEwen DG; Griffin KA; Koesters R; Weinberg JM; Bidani AK; Kriz W; Venkatachalam MA. 2012. PTEN loss defines a TGF-beta-induced tubule phenotype of failed differentiation and JNK signaling during renal fibrosis. Am J Physiol Renal Physiol 302(9):F1210-23. [PubMed: 22301622]  [MGI Ref ID J:183419]

Laronda MM; Unno K; Ishi K; Serna VA; Butler LM; Mills AA; Orvis GD; Behringer RR; Deng C; Sinha S; Kurita T. 2013. Diethylstilbestrol induces vaginal adenosis by disrupting SMAD/RUNX1-mediated cell fate decision in the Mullerian duct epithelium. Dev Biol 381(1):5-16. [PubMed: 23830984]  [MGI Ref ID J:200766]

Ma M; Tian X; Igarashi P; Pazour GJ; Somlo S. 2013. Loss of cilia suppresses cyst growth in genetic models of autosomal dominant polycystic kidney disease. Nat Genet 45(9):1004-12. [PubMed: 23892607]  [MGI Ref ID J:205308]

Perets R; Wyant GA; Muto KW; Bijron JG; Poole BB; Chin KT; Chen JY; Ohman AW; Stepule CD; Kwak S; Karst AM; Hirsch MS; Setlur SR; Crum CP; Dinulescu DM; Drapkin R. 2013. Transformation of the fallopian tube secretory epithelium leads to high-grade serous ovarian cancer in Brca;Tp53;Pten models. Cancer Cell 24(6):751-65. [PubMed: 24332043]  [MGI Ref ID J:207621]

Schietke RE; Hackenbeck T; Tran M; Gunther R; Klanke B; Warnecke CL; Knaup KX; Shukla D; Rosenberger C; Koesters R; Bachmann S; Betz P; Schley G; Schodel J; Willam C; Winkler T; Amann K; Eckardt KU; Maxwell P; Wiesener MS. 2012. Renal tubular HIF-2alpha expression requires VHL inactivation and causes fibrosis and cysts. PLoS One 7(1):e31034. [PubMed: 22299048]  [MGI Ref ID J:184217]

Stuart D; Rees S; Woodward SK; Koesters R; Strait KA; Kohan DE. 2012. Disruption of the endothelin A receptor in the nephron causes mild fluid volume expansion. BMC Nephrol 13:166. [PubMed: 23217151]  [MGI Ref ID J:196915]

Theilig F; Enke AK; Scolari B; Polzin D; Bachmann S; Koesters R. 2011. Tubular Deficiency of von Hippel-Lindau Attenuates Renal Disease Progression in Anti-GBM Glomerulonephritis. Am J Pathol 179(5):2177-88. [PubMed: 21925138]  [MGI Ref ID J:177371]

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 & HusbandryMutant mice were bred to C57BL/6J mice to generate this congenic strain. When maintaining the live congenic colony, hemizygous mice are bred with wildtype siblings or to C57BL/6J inbred mice.

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* $2140.00
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* $2782.00
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.

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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"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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