Strain Name:

B6;129-Mcl1tm3Sjk/J

Stock Number:

006088

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Availability:

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;129X1-Mcl1tm3Sjk/J    (Changed: 17-JAN-07 )
Type Mutant Stock; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Specieslaboratory mouse
 
Donating InvestigatorDr. Stanley J. Korsmeyer,   Dana-Farber Cancer Institute

Description
Mice that are homozygous for the targeted mutation are viable, normal in size, and do not display any gross physical or behavioral abnormalities. The donating investigator indicates that homozygous males have severely reduced fertility for unknown reasons, while females have normal fertility. Endogenous protein expression is unaffected by the inserted loxP sequences. When bred to mice with a cre recombinase gene under the control of a promoter of interest, exon 1 of the targeted gene is deleted in the tissue of interest. These mutant mice may be useful in studying global, temporal, or tissue-specific deletion of the endogenous gene, particularly in studies of immune function, including apoptosis, B and T cell development, and bone marrow cell differentiation.

When bred to a strain with the targeted null allele (Stock No. 006072) and a strain with a Cd19 null allele and expressing Cre recombinase during the B lymphocyte development (Stock No. 004126), this mutant mouse strain may be useful in studies of lymphocyte development.

When bred to a strain with the targeted null allele (Stock No. 006072) and a strain expressing interferon inducible Cre recombinase in the lymphocytes (Stock No. 003556), this mutant mouse strain may be useful in studies of lymphocyte development.

Development
A targeting vector was designed to insert a loxP site upstream of transcriptional start ATG of the endogenous gene. An additional targeting vector was then used to insert a loxP-flanked cytomegalovirus (CMV) promoter driving the expression of a hygromycin–thymidine kinase fusion protein (HYG-Tk) into intron 1 of the endogenous gene. This construct was electroporated into 129X1/SvJ-derived RW4 embryonic stem (ES) cells and then transiently transfected with CMV-Cre. Cre-mediated recombination resulting in a loxP-flanked exon 1 (and deletion of the HYG-Tk) were selected and injected into C57BL/6 blastocysts. Chimeric mice were crossed to C57BL/6 and the resulting heterozygotes were intercrossed to generate homozygotes prior to arrival at The Jackson Laboratory. These mice were crossed with "B6129F1" mice for at least one generation after arriving at The Jackson Laboratory.

Related Strains

Strains carrying other alleles of Mcl1
006072   B6.129X1-Mcl1tm2Sjk/J
View Strains carrying other alleles of Mcl1     (1 strain)

Additional Web Information

Introduction to Cre-lox technology

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.

Mcl1tm3Sjk/Mcl1tm3Sjk

        involves: 129X1/SvJ
  • normal phenotype
  • no abnormal phenotype detected
    • mice were viable and born at the expected Mendelian frequency   (MGI Ref ID J:86906)

The following phenotype relates to a compound genotype created using this strain.
Contact JAX® Services jaxservices@jax.org for customized breeding options.

Cd19tm1(cre)Cgn/Cd19+ Mcl1tm2Sjk/Mcl1tm3Sjk

        involves: 129P2/OlaHsd * 129X1/SvJ   (conditional)
  • hematopoietic system phenotype
  • abnormal B cell differentiation   (MGI Ref ID J:86906)
    • absent early pro-B cells   (MGI Ref ID J:86906)
    • absent late pro-B cells   (MGI Ref ID J:86906)
    • absent pre-B cells   (MGI Ref ID J:86906)
    • arrested B cell differentiation
      • arrested at pro-B cell stage   (MGI Ref ID J:86906)
  • decreased B cell number
    • decrease in peripheral B cells   (MGI Ref ID J:86906)
    • 88% reduction of splenic B cells relative to controls   (MGI Ref ID J:86906)
    • near absence of lymph node B cells   (MGI Ref ID J:86906)
    • detected peripheral B cells did not undergo cre-mediated recombination   (MGI Ref ID J:86906)
    • absent pre-B cells   (MGI Ref ID J:86906)
  • increased B cell apoptosis
    • increased apoptosis at pro-B cell stage   (MGI Ref ID J:86906)
  • immune system phenotype
  • abnormal B cell differentiation   (MGI Ref ID J:86906)
    • absent early pro-B cells   (MGI Ref ID J:86906)
    • absent late pro-B cells   (MGI Ref ID J:86906)
    • absent pre-B cells   (MGI Ref ID J:86906)
    • arrested B cell differentiation
      • arrested at pro-B cell stage   (MGI Ref ID J:86906)
  • decreased B cell number
    • decrease in peripheral B cells   (MGI Ref ID J:86906)
    • 88% reduction of splenic B cells relative to controls   (MGI Ref ID J:86906)
    • near absence of lymph node B cells   (MGI Ref ID J:86906)
    • detected peripheral B cells did not undergo cre-mediated recombination   (MGI Ref ID J:86906)
    • absent pre-B cells   (MGI Ref ID J:86906)
  • increased B cell apoptosis
    • increased apoptosis at pro-B cell stage   (MGI Ref ID J:86906)
  • cellular phenotype
  • increased B cell apoptosis
    • increased apoptosis at pro-B cell stage   (MGI Ref ID J:86906)

Mcl1tm2Sjk/Mcl1tm3Sjk Tg(Mx1-cre)1Cgn/0

        involves: 129X1/SvJ * C57BL/6 * CBA   (conditional)
  • hematopoietic system phenotype
  • decreased B cell number
    • peripheral B cells are not maintained   (MGI Ref ID J:86906)
  • decreased T cell number
    • peripheral T cells are not maintained   (MGI Ref ID J:86906)
  • immune system phenotype
  • decreased B cell number
    • peripheral B cells are not maintained   (MGI Ref ID J:86906)
  • decreased T cell number
    • peripheral T cells are not maintained   (MGI Ref ID J:86906)
View Research Applications

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

Apoptosis Research
Endogenous Regulators

Immunology, Inflammation and Autoimmunity Research
Autoimmunity
      B and T cell deficiency
Immunodeficiency
      B and T cell deficiency
Inflammation
      B and T cell deficiency
Lymphoid Tissue Defects
      B and T cell deficiency
      hematopoietic development

Reproductive Biology Research
Fertility Defects

Research Tools
Apoptosis Research
Cre-lox System
      loxP-flanked Sequences
Immunology, Inflammation and Autoimmunity Research
      B and T cell deficiency

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Mcl1tm3Sjk
Allele Name targeted mutation 3, Stanley J Korsmeyer
Allele Type Targeted (Conditional ready (e.g. floxed), No functional change)
Common Name(s) F-Mcl-1; Mcl-1f; Mcl-1flox;
Mutation Made ByDr. Stanley Korsmeyer,   Dana-Farber Cancer Institute
Strain of Origin129X1/SvJ
ES Cell Line NameRW-4
ES Cell Line Strain129X1/SvJ
Gene Symbol and Name Mcl1, myeloid cell leukemia sequence 1
Chromosome 3
Gene Common Name(s) AW556805; BCL2L3; EAT; MCL1-ES; MCL1L; MCL1S; Mcl-1; TM; bcl2-L-3; expressed sequence AW556805; mcl1/EAT;
Molecular Note Single loxP sites flank exon 1, which contains the start codon. Western blot analysis of lysates of thymocytes showed the level of protein in mutant mice to be comparable to that in wild-type mice. [MGI Ref ID J:86906]

Genotyping

Genotyping Information

Genotyping Protocols

Mcl1tm3Sjk, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Additional References

Mcl1tm3Sjk related

Ando T; Matsumoto K; Namiranian S; Yamashita H; Glatthorn H; Kimura M; Dolan BR; Lee JJ; Galli SJ; Kawakami Y; Jamora C; Kawakami T. 2013. Mast Cells Are Required for Full Expression of Allergen/SEB-Induced Skin Inflammation. J Invest Dermatol 133(12):2695-705. [PubMed: 23752044]  [MGI Ref ID J:202870]

Arac A; Grimbaldeston MA; Nepomuceno AR; Olayiwola O; Pereira MP; Nishiyama Y; Tsykin A; Goodall GJ; Schlecht U; Vogel H; Tsai M; Galli SJ; Bliss TM; Steinberg GK. 2014. Evidence that meningeal mast cells can worsen stroke pathology in mice. Am J Pathol 184(9):2493-504. [PubMed: 25134760]  [MGI Ref ID J:214825]

Arbour N; Vanderluit JL; Le Grand JN; Jahani-Asl A; Ruzhynsky VA; Cheung EC; Kelly MA; MacKenzie AE; Park DS; Opferman JT; Slack RS. 2008. Mcl-1 is a key regulator of apoptosis during CNS development and after DNA damage. J Neurosci 28(24):6068-78. [PubMed: 18550749]  [MGI Ref ID J:137346]

Campbell CJ; Lee JB; Levadoux-Martin M; Wynder T; Xenocostas A; Leber B; Bhatia M. 2010. The human stem cell hierarchy is defined by a functional dependence on Mcl-1 for self-renewal capacity. Blood 116(9):1433-42. [PubMed: 20525924]  [MGI Ref ID J:164522]

Germain M; Nguyen AP; Le Grand JN; Arbour N; Vanderluit JL; Park DS; Opferman JT; Slack RS. 2011. MCL-1 is a stress sensor that regulates autophagy in a developmentally regulated manner. EMBO J 30(2):395-407. [PubMed: 21139567]  [MGI Ref ID J:168794]

Hasan SM; Sheen AD; Power AM; Langevin LM; Xiong J; Furlong M; Day K; Schuurmans C; Opferman JT; Vanderluit JL. 2013. Mcl1 regulates the terminal mitosis of neural precursor cells in the mammalian brain through p27Kip1. Development 140(15):3118-27. [PubMed: 23824576]  [MGI Ref ID J:198626]

Kodama Y; Taura K; Miura K; Schnabl B; Osawa Y; Brenner DA. 2009. Antiapoptotic effect of c-Jun N-terminal Kinase-1 through Mcl-1 stabilization in TNF-induced hepatocyte apoptosis. Gastroenterology 136(4):1423-34. [PubMed: 19249395]  [MGI Ref ID J:148191]

Koss B; Morrison J; Perciavalle RM; Singh H; Rehg JE; Williams RT; Opferman JT. 2013. Requirement for antiapoptotic MCL-1 in the survival of BCR-ABL B-lineage acute lymphoblastic leukemia. Blood 122(9):1587-98. [PubMed: 23881917]  [MGI Ref ID J:202362]

Leveson-Gower DB; Sega EI; Kalesnikoff J; Florek M; Pan Y; Pierini A; Galli SJ; Negrin RS. 2013. Mast cells suppress murine GVHD in a mechanism independent of CD4+CD25+ regulatory T cells. Blood 122(22):3659-65. [PubMed: 24030387]  [MGI Ref ID J:204074]

Lilla JN; Chen CC; Mukai K; Benbarak MJ; Franco CB; Kalesnikoff J; Yu M; Tsai M; Piliponsky AM; Galli SJ. 2011. Reduced mast cell and basophil numbers and function in Cpa3-Cre; Mcl-1fl/fl mice. Blood 118(26):6930-8. [PubMed: 22001390]  [MGI Ref ID J:179080]

Malone CD; Hasan SM; Roome RB; Xiong J; Furlong M; Opferman JT; Vanderluit JL. 2012. Mcl-1 regulates the survival of adult neural precursor cells. Mol Cell Neurosci 49(4):439-47. [PubMed: 22357134]  [MGI Ref ID J:196735]

Marichal T; Starkl P; Reber LL; Kalesnikoff J; Oettgen HC; Tsai M; Metz M; Galli SJ. 2013. A beneficial role for immunoglobulin E in host defense against honeybee venom. Immunity 39(5):963-75. [PubMed: 24210352]  [MGI Ref ID J:208997]

Nauta AC; Grova M; Montoro DT; Zimmermann A; Tsai M; Gurtner GC; Galli SJ; Longaker MT. 2013. Evidence that mast cells are not required for healing of splinted cutaneous excisional wounds in mice. PLoS One 8(3):e59167. [PubMed: 23544053]  [MGI Ref ID J:199526]

Oka T; Kalesnikoff J; Starkl P; Tsai M; Galli SJ. 2012. Evidence questioning cromolyn's effectiveness and selectivity as a 'mast cell stabilizer' in mice. Lab Invest 92(10):1472-82. [PubMed: 22906983]  [MGI Ref ID J:189899]

Opferman JT; Iwasaki H; Ong CC; Suh H; Mizuno S; Akashi K; Korsmeyer SJ. 2005. Obligate role of anti-apoptotic MCL-1 in the survival of hematopoietic stem cells. Science 307(5712):1101-4. [PubMed: 15718471]  [MGI Ref ID J:96127]

Opferman JT; Letai A; Beard C; Sorcinelli MD; Ong CC; Korsmeyer SJ. 2003. Development and maintenance of B and T lymphocytes requires antiapoptotic MCL-1. Nature 426(6967):671-6. [PubMed: 14668867]  [MGI Ref ID J:86906]

Reber LL; Marichal T; Mukai K; Kita Y; Tokuoka SM; Roers A; Hartmann K; Karasuyama H; Nadeau KC; Tsai M; Galli SJ. 2013. Selective ablation of mast cells or basophils reduces peanut-induced anaphylaxis in mice. J Allergy Clin Immunol 132(4):881-8.e1-11. [PubMed: 23915716]  [MGI Ref ID J:205536]

Steimer DA; Boyd K; Takeuchi O; Fisher JK; Zambetti GP; Opferman JT. 2009. Selective roles for antiapoptotic MCL-1 during granulocyte development and macrophage effector function. Blood 113(12):2805-15. [PubMed: 19064728]  [MGI Ref ID J:146310]

Thomas RL; Roberts DJ; Kubli DA; Lee Y; Quinsay MN; Owens JB; Fischer KM; Sussman MA; Miyamoto S; Gustafsson AB. 2013. Loss of MCL-1 leads to impaired autophagy and rapid development of heart failure. Genes Dev 27(12):1365-77. [PubMed: 23788623]  [MGI Ref ID J:199154]

Wang X; Bathina M; Lynch J; Koss B; Calabrese C; Frase S; Schuetz JD; Rehg JE; Opferman JT. 2013. Deletion of MCL-1 causes lethal cardiac failure and mitochondrial dysfunction. Genes Dev 27(12):1351-64. [PubMed: 23788622]  [MGI Ref ID J:199155]

Woodland RT; Fox CJ; Schmidt MR; Hammerman PS; Opferman JT; Korsmeyer SJ; Hilbert DM; Thompson CB. 2008. Multiple signaling pathways promote B lymphocyte stimulator dependent B-cell growth and survival. Blood 111(2):750-60. [PubMed: 17942753]  [MGI Ref ID J:130058]

Xiang Z; Luo H; Payton JE; Cain J; Ley TJ; Opferman JT; Tomasson MH. 2010. Mcl1 haploinsufficiency protects mice from Myc-induced acute myeloid leukemia. J Clin Invest 120(6):2109-18. [PubMed: 20484815]  [MGI Ref ID J:161639]

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 & HusbandryWhen maintaining a live colony, these mice are bred as heterozygotes. Homozygous males have severely reduced fertility. As these mice are on a mixed B6;129X1 background, coat color variations may be observed in litters (including black, pink-eyed light chinchilla or albino).
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* $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.

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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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"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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