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. Species laboratory mouse   Donating Investigator Dr. 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 may relate to a genetic background differing from this JAX^® Mice strain.

Mcl1^tm3Sjk/Mcl1^tm3Sjk

        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.

Cd19^tm1(cre)Cgn/Cd19⁺ Mcl1^tm2Sjk/Mcl1^tm3Sjk

        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)
• 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
• 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)
• increased B cell apoptosis
  • increased apoptosis at pro-B cell stage   (MGI Ref ID J:86906)

Mcl1^tm2Sjk/Mcl1^tm3Sjk 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 and Inflammation 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 (Floxed/Frt)
Common Name(s)		F-Mcl-1; Mcl-1f; Mcl-1flox;
Mutation Made By		Dr. Stanley Korsmeyer,   Dana-Farber Cancer Institute
Strain of Origin		129X1/SvJ
ES Cell Line Name		RW-4
ES Cell Line Strain		129X1/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

Mcl1^tm3Sjk, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Additional References

Mcl1^tm3Sjk related

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]

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]

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]

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]

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]

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 & Husbandry	When 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

General Supply Notes

• Genomic DNA is available for this strain from the Mouse DNA Resource.

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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's Genotype Promise

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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