EXPERIMENTAL MODELS

Contributor Information
- Name Riccardo Dalla-Favera
- Institute The Trustees of Columbia University in the City of New York
Tool Details
- Tool name: MDR KO Mouse
- Tool type: Experimental models
- Tool sub-type: Mouse
- Disease: Chronic Lymphoblastic Leukemia
- Model: Knock-Out
- Model description: Knockout mouse of the MDR chromosomal region in m14qC3/h13q14, which encodes the DLEU2 gene and the miR15a/16-1 microRNA cluster
- Conditional: No
- Genetic background and cross history: A targeting vector was devised in order to flank MDR with frt-sites. DNA fragments of the 129/Sv-14qC3 were inserted into the targeting vector. Chimeras were obtained from correctly targeted ES cell colonies after injection of the targeted W9.5 ES clones (129/SvEvTac) into blastocysts derived from C57BL/6 mice, and gave rise to MDRfl/+ mice. The chimeras were then crossed with 129/SvCAGGS-Flpe to generate a MDR null allele
- Zygosity: Homozygous
- Strain: C57BL/6
- Description: Deletion of human chromosomal region 13q14 (mouse 14qC3) represents the most common genetic aberration in B-cell chronic lymphocytic leukaemia (CLL), a neoplasm of mature B lymphocytes. 13q14 deletions are commonly large and heterogeneous in size and affect multiple genes. Contained within the 13q14 region is the 0.11 megabase-long MDR, which encompasses the DLEU2 gene and miR-15a/16-1 cluster. Deletion of the MDR in this model organism recapitulates the full spectrum of CLL-associated lymphoproliferations in humans.
- Research area: Cancer; Immunology
- Production details: A targeting vector was devised in order to flank MDR with frt-sites. DNA fragments of the 129/Sv-14qC3 were inserted into the targeting vector. Chimeras were obtained from correctly targeted ES cell colonies after injection of the targeted W9.5 ES clones (129/SvEvTac) into blastocysts derived from C57BL/6 mice, and gave rise to MDRfl/+ mice. The chimeras were then crossed with 129/SvCAGGS-Flpe to generate a MDR null allele
- Additional notes: Knockout mouse of the MDR chromosomal region in m14qC3/h13q14, which encodes the DLEU2 gene and the miR15a/16-1 microRNA cluster
- For Research Use Only
References
- • Klein et al. 2010. Cancer Cell. 17(1):28-40. PMID: 20060366.
- • The DLEU2/miR-15a/16-1 cluster controls B cell proliferation and its deletion leads to chronic lymphocytic leukemia.