B6.129S(FVB)-Bcl6^tm1.1Dent/J

Stock number: 023727
Product name: Bcl6^fl
Research areas: Immunology, Inflammation and Autoimmunity Research, Research Tools

Description

Bcl6^fl/fl mice may be useful for studying the role of BCL6 in promoting T_FH cell differentiation and survival.

Detailed description

These Bcl6^fl/fl mutant mice possess loxP sites flanking exons 7-9 of the B cell leukemia/lymphoma 6 (Bcl6) gene. Bcl6 encodes a transcriptional repressor that regulates the differentiation of CD4 T cells into follicular Th cells (T_FH). Homozygotes are viable and fertile. When these mutant mice are bred to mice that express Cre recombinase, resulting offspring will have exons 7-9 deleted in cre-expressing tissues.

For example, when crossed to STOCK Tg(Cd4-cre)1Cwi/BfluJ mice (Stock No. 017336) expressing Cre recombinase in CD4-expressing T cells, double mutant mice exhibit almost complete loss of germinal center (GC) B cells and T_FH cells when immunized with sheep red blood cells.

Development

A targeting vector was designed to insert a single loxP site upstream of exon 7, and a loxP-flanked neomycin resistance (neo) cassette downstream of exon 9 of the B cell leukemia/lymphoma 6 (Bcl6) gene. The construct was electroporated into 129S/SvEv-Gpi1^c-derived CCE embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts and resulting chimeric males were bred with C57BL/6J females. Resulting offspring were bred to B6.FVB-Tg(EIIa-cre)C5379Lmgd/J transgenic mice (Stock No. 003724) to delete the neo cassette. Progeny contained multiple gene rearrangments; intact floxed-exons 7-9, intact floxed-neo cassette, or excision of exons 7-9 and the neo cassette. Offspring, containing only the floxed-exons 7-9, were bred to remove the cre-expressing transgene. These mice were bred to C57BL/6J mice for at least 6 generations. Upon arrival, mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the colony.

Allele

Symbol: Bcl6^tm1.1Dent
Name: targeted mutation 1.1, Alexander Dent
MGI accession ID: MGI:5518542
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); No functional change
Marker symbol: Bcl6
Marker name: B cell leukemia/lymphoma 6
Chromosome: 16
Strain of origin: 129S/SvEv-Gpi1^c
Molecular note: A targeting vector was designed to insert a single loxP site upstream of exon 7, and a loxP-flanked neomycin resistance (neo) cassette downstream of exon 9. Exons 7-9 encode the zinc finger domain. The neo selection cassette was subsequently removed from properly targeted mice by crossing to transgenic mice carrying Tg(EIIa-cre)C5379Lmgd.