Strain Name:

B6;SJL-Tg(MCL1)8Caig/J

Stock Number:

004187

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These transgenic mice express the human MCL1 under the direction of the human endogenous promoter. Mice exhibit enlarged spleens, increased total splenocyte number, lymph node enlargement and a high probability of developing lymphomas. This transgenic mouse strain may be useful in studies related to tumorigenesis and inhibition of tumorigenesis in the presence of a viability-promoting BCL2 family member.

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;J-Tg(MCL1)8Caig/J    (Changed: 15-DEC-04 )
B6;SJL-Tg(MCL1)8Caig    (Changed: 15-DEC-04 )
Type Mutant Stock; Transgenic;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Specieslaboratory mouse
 
Donating Investigator Ruth W. Craig,   Dartmouth Medical School

Description
These transgenic mice express the human MCL1 under the direction of the human MCL1 promoter. Expression of the human MCL1 protein was immunodetectable. Mice hemizygous for the transgene exhibited human MCL1 in bone marrow, lymph node, thymus and spleen (both B- and T-cell populations). Low levels of transgene expression was found in kidney, small intestine, uterus, lung and liver. The majority of the transgenic mice had enlarged spleens, with an increased total splenocyte number (both B- and T-cell). Transgenic mice displayed an increase of myeloid cells relative to lymphoid cells in bone marrow, and an enhanced viability of hematopoietic and lymphoid cells (B, T and myeloid) at immature and mature stages of development. In transgenic mice from 6 to 11 months of age, 27% displayed lymph node enlargement. Transgenic mice had an 88% probability of developing pathologic lymph node disease, and a 60% probability of developing disseminated disease from 6 months to 2 years of age. The lymphomas in the transgenic mice were predominantly of clonal B-cell origin and displayed a variety of histological subtypes including follicular lymphoma and diffuse large-cell lymphoma. This transgenic mouse strain represents a model that may be useful in studies related to tumorigenesis and inhibition of tumorigenesis in the presence of a viability-promoting BCL2 family member.

Development
A transgenic construct containing the entire human MCL1 gene, including the endogenous MCL1 promoter, was microinjected into B6;SJLF1 fertilized oocytes. Founder animals were bred to C57BL/6J mice.

Related Strains

Strains carrying   Tg(MCL1)8Caig allele
019576   B6.Cg-Tg(MCL1)8Caig/Mmjax
View Strains carrying   Tg(MCL1)8Caig     (1 strain)

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

Tg(MCL1)8Caig/0

        involves: C57BL/6 * SJL
  • immune system phenotype
  • abnormal immature B cell morphology
    • ratio of myeloid to B cell precursors is 2.2:1 versus 1.3:1 in wild-type bone marrow   (MGI Ref ID J:50604)
    • however, there is a 5-fold increase in the number of B cell precursors found in bone marrow culture compared to controls   (MGI Ref ID J:50604)
  • abnormal leukocyte physiology
    • myeloid cells present in splenocyte culture die-off at a slower rate than controls   (MGI Ref ID J:50604)
    • including IL-3 in the culture greatly enhanced survival of transgenic myeloid cells but not non-transgenic myeloid cells   (MGI Ref ID J:50604)
    • abnormal macrophage apoptosis
      • bone marrow derived macrophages have significantly less apoptosis than controls 20 hours after infection with pneumococcal infection   (MGI Ref ID J:95913)
      • by 48 hours after infection, apoptosis levels are similar to that in wild-type controls suggesting pneumococcal-associated apoptosis is delayed rather than suppressed   (MGI Ref ID J:95913)
    • decreased B cell apoptosis
      • B cells present in splenocyte culture die-off at about half the rate as wild-type B cells do   (MGI Ref ID J:50604)
    • decreased T cell apoptosis
      • T cells are still present after 3 days of splenocyte culture compared to no T cells surviving culture of wild-type splenocytes   (MGI Ref ID J:50604)
  • abnormal mast cell differentiation
    • immortalized immature mast cells can be cultured out of spleens with a frequency of 3 x 10-5, which is at least 1000-fold more frequent than controls   (MGI Ref ID J:50604)
  • abnormal monocyte differentiation
    • immortalized monocytes can be cultured of out of spleens unlike with wild-type controls   (MGI Ref ID J:50604)
  • decreased splenocyte apoptosis
    • 25% of splenocytes survive four days of culture while all of controls die   (MGI Ref ID J:50604)
    • cultured splenocytes die off at a rate about half that of controls   (MGI Ref ID J:50604)
  • increased spleen white pulp amount
    • mice rarely have expansion of the white pulp   (MGI Ref ID J:50604)
  • increased susceptibility to bacterial infection
    • pneumococcal-associated macrophage apoptosis is lower by about half in these mice 14 hours after infection   (MGI Ref ID J:95913)
    • mice fail to clear bacteria after infection with 104 CFU compared to controls   (MGI Ref ID J:95913)
    • all transgenic mice with more than 102 CFU in the lung develope bacteremia, which does not occur in nontransgenic mice   (MGI Ref ID J:95913)
    • at higher infection doses, the amount of CFUs in the lung is a log unit higher than that in wild-type mice   (MGI Ref ID J:95913)
  • increased thymocyte number
    • 2 of 9 mice have increased numbers of thymocytes   (MGI Ref ID J:50604)
  • spleen hyperplasia
    • spleens have 1.6-fold higher number of cells and are visibly larger   (MGI Ref ID J:50604)
  • hematopoietic system phenotype
  • abnormal common myeloid progenitor cell morphology   (MGI Ref ID J:69755)
    • there is a doubling in the number of myeloid progenitors found in the bone marrow   (MGI Ref ID J:50604)
    • these progenitors exhibit enhanced survival in the absence of growth factors   (MGI Ref ID J:50604)
  • abnormal immature B cell morphology
    • ratio of myeloid to B cell precursors is 2.2:1 versus 1.3:1 in wild-type bone marrow   (MGI Ref ID J:50604)
    • however, there is a 5-fold increase in the number of B cell precursors found in bone marrow culture compared to controls   (MGI Ref ID J:50604)
  • abnormal leukocyte physiology
    • myeloid cells present in splenocyte culture die-off at a slower rate than controls   (MGI Ref ID J:50604)
    • including IL-3 in the culture greatly enhanced survival of transgenic myeloid cells but not non-transgenic myeloid cells   (MGI Ref ID J:50604)
    • abnormal macrophage apoptosis
      • bone marrow derived macrophages have significantly less apoptosis than controls 20 hours after infection with pneumococcal infection   (MGI Ref ID J:95913)
      • by 48 hours after infection, apoptosis levels are similar to that in wild-type controls suggesting pneumococcal-associated apoptosis is delayed rather than suppressed   (MGI Ref ID J:95913)
    • decreased B cell apoptosis
      • B cells present in splenocyte culture die-off at about half the rate as wild-type B cells do   (MGI Ref ID J:50604)
    • decreased T cell apoptosis
      • T cells are still present after 3 days of splenocyte culture compared to no T cells surviving culture of wild-type splenocytes   (MGI Ref ID J:50604)
  • abnormal mast cell differentiation
    • immortalized immature mast cells can be cultured out of spleens with a frequency of 3 x 10-5, which is at least 1000-fold more frequent than controls   (MGI Ref ID J:50604)
  • abnormal monocyte differentiation
    • immortalized monocytes can be cultured of out of spleens unlike with wild-type controls   (MGI Ref ID J:50604)
  • decreased splenocyte apoptosis
    • 25% of splenocytes survive four days of culture while all of controls die   (MGI Ref ID J:50604)
    • cultured splenocytes die off at a rate about half that of controls   (MGI Ref ID J:50604)
  • extramedullary hematopoiesis
    • extramedullary hematopoiesis is very active in these mice   (MGI Ref ID J:50604)
  • increased erythroid progenitor cell number
    • there is a doubling in the number of erythroid progenitors found in the bone marrow   (MGI Ref ID J:50604)
    • these progenitors exhibit enhanced survival in the absence of growth factors   (MGI Ref ID J:50604)
  • increased spleen white pulp amount
    • mice rarely have expansion of the white pulp   (MGI Ref ID J:50604)
  • increased thymocyte number
    • 2 of 9 mice have increased numbers of thymocytes   (MGI Ref ID J:50604)
  • spleen hyperplasia
    • spleens have 1.6-fold higher number of cells and are visibly larger   (MGI Ref ID J:50604)
  • tumorigenesis
  • increased lymphoma incidence
    • about 27% of mice at 6-11 months of age develop lymphomas of various subtypes   (MGI Ref ID J:69755)
    • lymphomas develop in about 50% of transgenic mice at 18 to 23 months of age and in about 65% of mice at 2 years of age compared to 12% of non-transgenic mice by 2 years of age   (MGI Ref ID J:69755)
    • two-thirds of the cases involve disseminated disease affecting lymph nodes (mesenteric, renal, mediastinal, and cervical areas) and other tissues (liver, lung, kidney)   (MGI Ref ID J:69755)
    • in the remaining one third of affected transgenic animals, disease was localized to mesenteric lymph nodes or presented as extra-nodal lymphoma in the gastrointestinal tract   (MGI Ref ID J:69755)
    • increased T cell derived lymphoma incidence
      • non-disseminated T cell lymphoma occurred in 1 case out of 18 total lymphoma cases   (MGI Ref ID J:69755)
    • increased follicular lymphoma incidence
      • the majority of lymphomas are diffuse large-cell lymphoma with B-cell origins or indeterminate origin   (MGI Ref ID J:69755)
      • some cases present a polymorphic cytology consisting of a heterogeneous mixture of small and large lymphocytes   (MGI Ref ID J:69755)
      • B cells lacking IgM expression constitute the majority of the large cells in the cases of disseminated disease   (MGI Ref ID J:69755)
      • Ig-heavy chain analysis of lymphomas reveals clonal rearrangement of the immunoglobulin heavy-chain locus (except in the one case of T cell lymphoma) demonstrating a B cell origin   (MGI Ref ID J:69755)
  • cellular phenotype
  • abnormal macrophage apoptosis
    • bone marrow derived macrophages have significantly less apoptosis than controls 20 hours after infection with pneumococcal infection   (MGI Ref ID J:95913)
    • by 48 hours after infection, apoptosis levels are similar to that in wild-type controls suggesting pneumococcal-associated apoptosis is delayed rather than suppressed   (MGI Ref ID J:95913)
  • abnormal mast cell differentiation
    • immortalized immature mast cells can be cultured out of spleens with a frequency of 3 x 10-5, which is at least 1000-fold more frequent than controls   (MGI Ref ID J:50604)
  • abnormal monocyte differentiation
    • immortalized monocytes can be cultured of out of spleens unlike with wild-type controls   (MGI Ref ID J:50604)
  • decreased B cell apoptosis
    • B cells present in splenocyte culture die-off at about half the rate as wild-type B cells do   (MGI Ref ID J:50604)
  • decreased T cell apoptosis
    • T cells are still present after 3 days of splenocyte culture compared to no T cells surviving culture of wild-type splenocytes   (MGI Ref ID J:50604)
  • decreased splenocyte apoptosis
    • 25% of splenocytes survive four days of culture while all of controls die   (MGI Ref ID J:50604)
    • cultured splenocytes die off at a rate about half that of controls   (MGI Ref ID J:50604)
  • endocrine/exocrine gland phenotype
  • increased thymocyte number
    • 2 of 9 mice have increased numbers of thymocytes   (MGI Ref ID J:50604)
View Research Applications

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

Cancer Research
Increased Tumor Incidence
      Lymphomas

MCL1 related

Apoptosis Research
Endogenous Regulators

Cancer Research
Increased Tumor Incidence
      Leukemia

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Tg(MCL1)8Caig
Allele Name transgene insertion 8, Ruth W Craig
Allele Type Transgenic (Inserted expressed sequence)
Mutation Made By Ruth Craig,   Dartmouth Medical School
Strain of Origin(C57BL/6 x SJL)F1
Expressed Gene MCL1, myeloid cell leukemia 1, human
Promoter MCL1, myeloid cell leukemia 1, human
Molecular Note The transgene contains the entire human MCL1 gene, including the endogenous MCL1 promoter. Hemizygous transgenic mice expressed human MCL1 in bone marrow, lymph node, thymus, and spleen (both B- and T-cell populations). Low levels of transgene expression were found in the kidney, small intestine, uterus, lung and liver. [MGI Ref ID J:50604]
 

Genotyping

Genotyping Information

Genotyping Protocols

Tg(MCL1)8Caig-alternate1, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Zhou P; Qian L; Bieszczad CK; Noelle R; Binder M; Levy NB; Craig RW. 1998. Mcl-1 in transgenic mice promotes survival in a spectrum of hematopoietic cell types and immortalization in the myeloid lineage. Blood 92(9):3226-39. [PubMed: 9787159]  [MGI Ref ID J:50604]

Additional References

Zhou P; Levy NB; Xie H; Qian L; Lee CY; Gascoyne RD; Craig RW. 2001. MCL1 transgenic mice exhibit a high incidence of B-cell lymphoma manifested as a spectrum of histologic subtypes. Blood 97(12):3902-9. [PubMed: 11389033]  [MGI Ref ID J:69755]

Tg(MCL1)8Caig related

Gui J; Morales AJ; Maxey SE; Bessette KA; Ratcliffe NR; Kelly JA; Craig RW. 2011. MCL1 increases primitive thymocyte viability in female mice and promotes thymic expansion into adulthood. Int Immunol 23(10):647-59. [PubMed: 21937457]  [MGI Ref ID J:177131]

Marriott HM; Bingle CD; Read RC; Braley KE; Kroemer G; Hellewell PG; Craig RW; Whyte MK; Dockrell DH. 2005. Dynamic changes in Mcl-1 expression regulate macrophage viability or commitment to apoptosis during bacterial clearance. J Clin Invest 115(2):359-68. [PubMed: 15650769]  [MGI Ref ID J:95913]

Zhou P; Levy NB; Xie H; Qian L; Lee CY; Gascoyne RD; Craig RW. 2001. MCL1 transgenic mice exhibit a high incidence of B-cell lymphoma manifested as a spectrum of histologic subtypes. Blood 97(12):3902-9. [PubMed: 11389033]  [MGI Ref ID J:69755]

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 transgenic strain was created on a B6;SJLF1 background. Founder animals were bred to normal C57BL/6J mice to produce hemizygotes. These mice are maintained by mating hemizygotes. Female homozygotes are fertile and do not mate.

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.

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 willfulfill 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.

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 willfulfill 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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