Description

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 Mutant Mice. Species laboratory mouse Generation N?+1   Donating Investigator Ruth 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.

Phenotype

Phenotype Information

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

Allele Symbol		Tg(MCL1)8Caig
Allele Name		transgene insertion 8, Ruth W Craig
Allele Type		Transgenic (random, expressed)
Mutation Made By		Ruth Craig,   Dartmouth Medical School
Strain of Origin		involves: C57BL/6 * SJL
Expressed Gene		MCL1, myeloid cell leukemia sequence 1 (BCL2-related), human
Promoter		MCL1, myeloid cell leukemia sequence 1 (BCL2-related), human
General Note		Hemizygous transgenic mice exhibit human MCL1 in bone marrow, lymph node, thymus, and spleen (both B- and T-cell populations). Low levels of transgene expression is found in kidney, small intestine, uterus, lung and liver. The majority of the transgenic mice have enlarged spleens, with an increased total splenocyte number (both B- and T-cell). Transgenic mice display an increase of myeloid cells relative to lymphoid cells in bone marrow, and an enhanced viability of hematopoietic and lymphoid cells (B, Tand 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 have 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 ware predominantly of clonal B-cell origin and display a variety of histological subtypes including follicular lymphoma and diffuse large-cell lymphoma.
Molecular Note		The transgene contains the entire human MCL1 gene, including the endogenous MCL1 promoter. [MGI Ref ID J:50604]

Genotyping

Genotyping Information

This strain will not have a genotyping protocol or one is not currently available.

Helpful Links

Optimizing PCR Protocols

References

References

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

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

Health & Colony Maintenance Information

Colony Maintenance

Breeding & Husbandry	This 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.

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Supply Details

Standard Supply

Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information.

Supply Notes

Cryorecovery - Standard. The recovery process begins when a signed agreement form is returned to the Customer Service Department after order placement. Although results vary by strain, at least two males and two females (two pairs) will be provided, typically within 15 weeks of our receipt of the signed agreement form. If the first recovery attempt is unsuccessful or only one pair is recovered, a second recovery will be done, extending the delivery time to approximately 25 weeks. At least one member of each pair will be of known genotype and will carry the mutation if it is a mutant strain. Please note that pairs may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation of the strain. Mating schemes are sometimes modified for successful cryopreservation. Price represents a repository maintenance fee, which includes the cost of recovery of the strain from the cryopreservation resource and the periodic replacement of the frozen embryos used for recovery. Cryorecovery to establish a Dedicated Supply for greater quantities of mice. One to two pairs will be recovered to establish a Dedicated Supply of mice. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 or 1-207-288-5845. This strain is included in the Induced Mutant Resource Colony collection.

General Terms and Conditions

See Terms of Use

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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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Terms of Use

Terms of Use

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