B6.129S1-Is(14C3)3Rdf/J

Stock number: 017643
Research areas: Cancer Research, Research Tools

Description

These 14qC3-CDR^fl mice carry a floxed segment that encompasses sequence corresponding to a common deleted region (CDR) 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.

Detailed description

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. A 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. The CDR, common deleted region, contains the 0.11Mb minimal deleted region (MDR) as well as a 0.69Mb genomic region telomeric to the MDR. These mice carry the conditional (floxed) CDR, common deleted region, allele. loxP and FRT sites flank a 0.8 mb region that includes the Dleu5, Kcnrg, Dleu2 genes, Mir15a/Mir16-1 cluster, Dleu7, and Rnaseh2b genes. Homozygotes 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).

Development

To generate the CDR^fl/+ allele, a targeting vector containing TK gene, an eGFP minigene, a triple SV40 polyA site, 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 Dleu5 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 2 kb centromeric to the last exon of Gucy1b2 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

Symbol: Is(14)5Rdf
Name: insertion, Chr 14, Riccardo Dalla-Favera 5
MGI accession ID: MGI:5304347
Generation method: Targeted
Marker symbol: Is(14)5Rdf
Marker name: insertion, Chr 14, Riccardo Dalla-Favera 5
Chromosome: 14
Strain of origin: 129S1/Sv-Oca2⁺ Tyr⁺ Kitl⁺
Site of expression: When bred to a strain with Cre recombinase, expression occurs in B lymphocytes.
Molecular note: The targeting vector contained a PGK-Hygro cassette, loxP and FRT sites, inserted in the telomeric region of 14qC3, approximately 2 kb centromeric to the last exon of Rnaseh2b gene.
General note: This allele was originally generated in cis with Is(14)1Rdf.