EXPERIMENTAL MODELS

Contributor Information
- Name Riccardo Dalla-Favera
- Institute The Trustees of Columbia University in the City of New York
Tool Details
- Tool name: IMu-HA-BCL6 Mouse
- Alternate names: Zinc Finger Protein 51, B Cell CLL/Lymphoma 6, Protein LAZ-3
- Tool type: Experimental models
- Tool sub-type: Mouse
- Disease: Diffuse Large B-Cell Lymphoma
- Model: Knock-In
- Conditional: No
- Genetic background and cross history: The IHABCL6 targeting vector was constructed by subcloning a HA-tagged murine BCL6 cassette into the pPNT vector, downstream of the IgH I promoter (1.1Kb PCR fragment) and 5' to a loxP-flanked stop cassette containing a neomycin-resistance gene (neoR). A ~10 Kb EcoRI fragment including the four C exons was then isolated from pEco1.1C vector and subcloned downstream to the neoR cassette. The targeting vector was electroporated in the ES cell line 129/Sv, and Neo-resistant, homologous recombinant clones were identified. After Cre mediated excision of the neoR cassette in vitro by transient transfection of a Cre-expressing plasmid, homologous recombinant ES cell clones were injected into blastocysts from C57BL/6 mice. Chimeric mice obtained from ES clones transmitted the knockin allele through the germline and were all backcrossed onto a C57BL/6 background (18 generations)
- Phenotype: Knockin mouse expressing BCL6 constitutively in B cells under control of the immunoglobulin I promotor
- Zygosity: Homozygous
- Strain: C57BL/6
- Description: Diffuse Large B-Cell Lymphoma (DLBCL) is a B-Cell non-Hodgkins Lymphoma, the fifth most common cancer in the western world. DLBCL is a poorly understood and aggressive disease with ongoing research for the development of effective therapies. This mouse model mimics a chromosomal translocation found in approximately 50% of human DLBCL cases.
- Research area: Cancer; Immunology
- Production details: The IÎźHABCL6 targeting vector was constructed by subcloning a HA-tagged murine BCL6 cassette into the pPNT vector, downstream of the IgH IÎź promoter (1.1Kb PCR fragment) and 5Ⲡto a loxP-flanked stop cassette containing a neomycin-resistance gene (neoR). A âź10 Kb EcoRI fragment including the four CÎź exons was then isolated from pEco1.1CÎź vector and subcloned downstream to the neoR cassette. The targeting vector was electroporated in the ES cell line 129/Sv, and Neo-resistant, homologous recombinant clones were identified. After Cre mediated excision of the neoR cassette in vitro by transient transfection of a Cre-expressing plasmid, homologous recombinant ES cell clones were injected into blastocysts from C57BL/6 mice. Chimeric mice obtained from ES clones transmitted the knockin allele through the germline and were all backcrossed onto a C57BL/6 background (1â8 generations)
- Additional notes: Knockin mouse expressing BCL6 constitutively in B cells under control of the immunoglobulin IÂľ promotor
- For Research Use Only
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References
- • Cattoretti et al. 2005. Cancer Cell. 7(5):445-55. PMID: 15894265.
- • Deregulated BCL6 expression recapitulates the pathogenesis of human diffuse large B cell lymphomas in mice.