B6;129-Bcl9^tm1.1Agt Bcl9l^tm1.1Agt/J

Stock number: 027388
Product name: BCL9/9-2^flox
Strain synonyms: Bcl9/9l^flox
Research areas: Cell Biology Research, Research Tools

Description

Bcl9/9l^flox mice may be useful for studying divergent phenotypes resulting from impaired Wnt signaling during development and during adult tissue repair.

Detailed description

Bcl9/9l^flox mutant mice possess loxP sites flanking exons of the B cell CLL/lymphoma 9 (Bcl9) gene and exons of the Bcl9 homolog, Bcl9l. Specifically, exon 5 of Bcl9, which encodes the β-catenin binding site, was flanked with loxP sites. Likewise, exons 6-7 of Bcl9l, encoding the β-catenin and Pygopus binding sites, were flanked with loxP sites. BCL9 and BCL9-2 may have some functional redundancy. Bcl9/9l signals downstream of Wnt-induced transcriptional regulation, where it interacts with transcriptional co-activators Pygopus and β-catenin. Wnt signaling is involved in the regulation of gene transcription during embryonic development and adult tissue renewal. BCL9 is essential for regulating Wnt signaling during specific stages of adult muscle stem cell activation. Mice that are homozygous for both alleles are viable and fertile. When bred to mice that express tissue-specific Cre recombinase, resulting offspring will have the floxed exons deleted in the cre-expressing tissues.

When bred to B6;129-Myf5^tm1(cre)Mrc/J mice (Stock No. 010529) expressing Cre Recombinase in myoblast progenitors of skeletal muscle lineage, double mutant offspring display normal muscle development. After injury these mice exhibit impaired muscle regeneration and decreased muscle fiber size.

When bred to mice expressing Cre Recombinase in intestinal epithelium, double mutant offspring showed decreased expression of Wnt-regulated genes and impaired regeneration of ulcerated colon epithelium. They also develop adenocarcinomas lacking epithelial-mesenchymal transition (EMT) and stem cell–like properties.

Development

A targeting vector was designed to insert a loxP site, followed by a frt-flanked neomycin resistance (neo) cassette, upstream of exon 5 and a second loxP site downstream of exon 5 of the B cell CLL/lymphoma 9 (Bcl9) gene.

A second targeting vector was designed to insert a loxP site upstream of exon 6, followed by a frt-flanked neomycin resistance (neo) cassette, and a second loxP site downstream of exon 7 of the B cell CLL/lymphoma 9-like (Bcl9l) gene.

These constructs were electroporated into 129/Sv-derived GS-1 embryonic stem (ES) cells. Correctly targeted ES cells, containing both alleles, were injected into C57BL/6xDBA2 blastocysts and resulting chimeric mice were bred with B6.129S4-Gt(ROSA)26Sor^tm1(FLP1)Dym/RainJ transgenic mice (Stock No. 009086) to delete the neo cassette. Progeny were crossed to remove the Flp-expressing transgene, and resulting colony was maintained on a mixed background. Upon arrival, mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the colony.

Allele

Symbol: Bcl9l^tm1.1Agt
Name: targeted mutation 1.1, Michel Aguet
MGI accession ID: MGI:4398981
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); No functional change
Marker symbol: Bcl9l
Marker name: B cell CLL/lymphoma 9-like
Chromosome: 9
Strain of origin: 129/Sv
Molecular note: Exons 6 and 7 were floxed and the inserted frt flanked neo cassette was removed by germ line, flp mediated recombination.

Allele

Symbol: Bcl9^tm1.1Agt
Name: targeted mutation 1.1, Michel Aguet
MGI accession ID: MGI:4398979
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); No functional change
Marker symbol: Bcl9
Marker name: B cell CLL/lymphoma 9
Chromosome: 3
Strain of origin: 129/Sv
Molecular note: Exon 5 was floxed, and the inserted frt flanked neo cassette was removed by germ line, flp mediated recombination.