These Mll-CbpSTOP mice may be useful when studying the role of the chromosomal translocation MLL-CBP t(11;16)(q23;p13) on therapy-induced myeloproliferative diseases.
James J. Hsieh, Memorial Sloan-Kettering Cancer Center
Genetic Background | Generation |
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|
Allele Type | Gene Symbol | Gene Name |
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Targeted (Inserted expressed sequence) | Kmt2a | lysine (K)-specific methyltransferase 2A |
These Mll-CbpSTOP mice carry a floxed STOP cassette upstream of exon 8 of the myeloid/lymphoid or mixed-lineage leukemia 1 (Mll1) gene, and a CREB binding protein (Cbp) cDNA, a Simian virus 40 polyadenylation signal (SV40 pA), and a puromycin resistance sequence (puro) in Mll1 exon 8. Mice that are heterozygous for the targeted mutation are viable and fertile with no Mll-Cbp fusion protein expression detected. Homozygous mice are not viable. The MLL-CBP fusion protein is a characteristic of the t(11;16)(q23;p13) chromosomal translocation found in patients with therapy-induced myeloproliferative diseases, including acute myelomonocytic leukemia (t-AMML), chronic myelomonocytic leukemia (t-CMML), and myelodysplastic syndrome (t-MDS).
When bred to mice that express interferon-inducible Cre recombinase (see Stock No. 003556), resulting offspring treated with polyinosinic-polycytidylic acid (pI-pC) will have the floxed-STOP cassette deleted in the cre-expressing tissues. This allows the expression of the MLL-CBP in cre-expressing tissue. These mice exhibit a three-fold reduction in common lymphoid progenitors (CLPs) and a 3-fold increase in myeloid progenitors, with enhanced proliferation, in bone marrow. This myeloid hyperplasia is evident within days of MLL-CBP expression. Subsequent γ-irradiation or N-ethyl-N-nitrosourea (ENU) treatment results in the onset of a spectrum of myeloproliferative disease and decreased survival.
A targeting vector was designed to insert a loxP-flanked stop cassette upstream of exon 8 of the myeloid/lymphoid or mixed-lineage leukemia 1 (Mll1) gene. A cassette containing 6.5-kb fragment of murine CREB binding protein (Cbp) cDNA, a Simian virus 40 polyadenylation signal (SV40 pA), and a puromycin resistance sequence (puro) was inserted into Mll1 exon 8. The construct was electroporated into 129X1/SvJ-derived RW4 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts and the resulting chimeric males were bred to C57BL/6 females. Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6J (Stock No. 000664) for at least one generation to establish the colony.
Expressed Gene | Crebbp, CREB binding protein, mouse, laboratory |
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Expressed Gene | Kmt2a, lysine (K)-specific methyltransferase 2A, mouse, laboratory |
Site of Expression | A Kmt2a-Crebbp (Mll-Cbp) fusion protein is expressed in cre-expressing tissues after these mice are bred with mice carrying cre recombinase. |
Allele Name | targeted mutation 2, Stanley J Korsmeyer |
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Allele Type | Targeted (Inserted expressed sequence) |
Allele Synonym(s) | Mll-CbbSTOP |
Gene Symbol and Name | Kmt2a, lysine (K)-specific methyltransferase 2A |
Gene Synonym(s) | |
Expressed Gene | Crebbp, CREB binding protein, mouse, laboratory |
Expressed Gene | Kmt2a, lysine (K)-specific methyltransferase 2A, mouse, laboratory |
Site of Expression | A Kmt2a-Crebbp (Mll-Cbp) fusion protein is expressed in cre-expressing tissues after these mice are bred with mice carrying cre recombinase. |
Strain of Origin | 129X1/SvJ |
Chromosome | 9 |
Molecular Note | A targeting vector was designed to insert a loxP-flanked stop cassette upstream of exon 8 of the lysine (K)-specific methyltransferase 2A (Kmt2a) gene. A cassette containing 6.5-kb fragment of murine CREB binding protein (Cbp) cDNA, a Simian virus 40 polyadenylation signal (SV40 pA), and a puromycin resistance sequence (puro) was inserted into exon 8. |
When maintaining a live colony, heterozygous mice may be bred to wildtype mice from the colony or to C57BL/6J inbred mice (Stock No. 000664).
When using the B6;129X1-Kmt2atm2Sjk/JjdhJ mouse strain in a publication, please cite the originating article(s) and include JAX stock #021296 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
---|---|---|
Heterozygous or Wildtype for Kmt2a<tm2Sjk> |
Frozen Mouse Embryo | B6;129X1-Kmt2a<tm2Sjk>/JjdhJ Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | B6;129X1-Kmt2a<tm2Sjk>/JjdhJ Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | B6;129X1-Kmt2a<tm2Sjk>/JjdhJ Frozen Embryo | $3373.50 |
Frozen Mouse Embryo | B6;129X1-Kmt2a<tm2Sjk>/JjdhJ Frozen Embryo | $3373.50 |
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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. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.
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