B6;129-Fbxw7^tm1Iaai/J

Stock number: 017563
Product name: Fbw7^flox
Research areas: Cancer Research, Hematological Research, Research Tools

Description

These floxed mutant mice possess loxP sites flanking exons 5 and 6 of the Fbw7 gene. This strain may be useful in generating conditional mutants to study ubiquitin ligase, hematopoietic stem cell self-renewal/differentiation and tumor suppression.

Detailed description

These Fbw7^f/f mice possess loxP sites flanking exons 5 and 6. These exons encode the F-box domain required for ubiquitination complex assembly. As a ubiquitin ligase, Fbwx7 is involved in targeting the cell cycle regulators c-Myc and Notch1 for proteasomal degradation. Mice that are homozygous for the targeted mutation are viable, fertile and normal in size. When used in conjunction with a Cre recombinase-expressing strain, this strain is useful in generating tissue-specific mutants of the floxed allele. This mutant mouse strain may be useful in generating conditional mutations to study regulation of hematopoietic stem cells and tumor suppression.

For example, when crossed to a strain expressing interferon-inducible Cre recombinase (see Stock No. 003556), mice exhibit impaired hematopoietic stem cell self-renewal and differentiation.

Development

A targeting vector was designed to place a loxP site upstream of exon 5 and an FRT-flanked neomycin resistance cassette followed by a loxP site downstream of exon 6. The construct was electroporated into 129/SvEn x C57BL/6-derived embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. Strong chimeras were identified and crossed to C57BL/6 females to verify germline transmission. The F1 generation was PCR screened and crossed to 129S4/SvJaeSor-Gt(ROSA)26Sor^tm1(FLP1)Dym/J (Stock No. 003946) to remove the neo cassette and then further backcrossed to C57BL/6 for at least three generations. At some point, the Fbw7^f colony was bred to Mx1-Cre mice (see Stock No. 003556). In 2012, the Fbw7^f/f mice (B6;129 genetic background) were sent to The Jackson Laboratory. Upon arrival, mice were bred to C57BL/6J for at least one generation to establish our Fbw7^f colony. The Cre-expressing allele was bred away from our live colony.

Allele

Symbol: Fbxw7^tm1Iaai
Name: targeted mutation 1, Iannis Aifantis
MGI accession ID: MGI:3798866
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); No functional change
Marker symbol: Fbxw7
Marker name: F-box and WD-40 domain protein 7
Chromosome: 3
Strain of origin: 129/Sv x C57BL/6
Molecular note: A loxP site was inserted downstream of exon 4 and an frt- and loxP-flanked neo cassette was inserted downstream of exon 6. Germ line, frt-mediated recombination was used to remove the neo cassette leaving exons 5 and 6 floxed.