These 14qC3-MDR mice carry a floxed region that encompases a region corresponding to a minimal deleted region involved in most common B cell chronic lymphocytic leukemias in humans. They have applications in studies related to tumorigenesis and therapeutic management of chronic lymphocytic leukemia.
Ulf Klein, University of Leeds
In B cell chronic lymphocytic leukemia the most common genomic aberration is deletion of human chromosomal region 13q14, corresponding to mouse chromosomal region 14qC3. Deletions of this same region are also found in monoclonal B-cell lymphocytosis and diffuse large B-cell lymphomas. An 0.11Mb minimal deleted region (MDR), that includes DLEU2 (deleted in lymphocytic leukemia, 2) and the MIR15A/MIR16-1 cluster, has been identified in more than half the patients with B cell chronic lymphocytic leukemia. These mice carry the conditional (floxed) MDR (minimal deleted region) allele, 14qC3-MDR. loxP and FRT sites flank a 110 kb region that includes the Dleu5, Kcnrg, Dleu2 genes and Mir15a/Mir16-1 cluster. Mice that are homozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. Cre-mediated recombination is indicated by GFP expression.
When bred to a strain with Cre recombinase expression in B lymphocytes (see Stock No. 006785 for example), this mutant mouse strain may be useful in studies of chronic lymphocytic leukemia (CLL).
To generate the 14qC3-MDR allele, a targeting vector containing TK gene, an eGFP minigene, a triple SV40 polyA site (tpA), a PGK-NEO cassette, and loxP and FRT sites was inserted in the centromeric region of the 14qC3 locus, approximately 20 kb centromeric to the Dleu2 gene. The construct was electroporated into 129S1/Sv-Oca2+ Tyr+ Kitl+ derived W9.5 embryonic stem (ES) cells. Correctly targeted ES cells were targeted again with a targeting vector, containing a PGK-Hygro cassette, loxP and FRT sites, inserted in the telomeric region of 14qC3, approximately 5 kb telomeric to exon 1b of the Dleu2 gene. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric animals were crossed to C57BL/6 mice, and then backcrossed to C57BL/6 for 10 generations.
Upon arrival at The Jackson Laboratory, the mice were crossed to C57BL/6J (Stock No. 000664) at least once to establish the colony.
|Allele Name||insertion, Chr 14, Riccardo Dalla-Favera 2|
|Allele Type||Targeted (Conditional ready (e.g. floxed), No functional change)|
|Gene Symbol and Name||Is(14)2Rdf, insertion, Chr 14, Riccardo Dalla-Favera 2|
|Site of Expression||Cre recombination results in EGFP expression in cre-expressing tissues.|
|Strain of Origin||129S1/Sv-Oca2+ Tyr+ Kitl+|
|Molecular Note||LoxP and FRT sites as well as a PGK promoter and Hygro cassette were place about 5 kb telomeric to the alternative exon 1 of Dleu2 by homologous recombination. The targeting was done in ES cells carrying |
|Mutations Made By|| |
Ulf Klein, University of Leeds
When maintaining a live colony, these mice can be bred as homozygotes.
When using the B6.129S1-Is(14)2Rdf/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #017642 in your Materials and Methods section.