B6.129-Fto^tm1.1Pzg/YxtJ

Stock number: 027830
Product name: Fto^flox
Research areas: Cell Biology Research, Metabolism Research, Research Tools

Description

Fto^flox mice have loxP sites flanking exon 3 of the fat mass and obesity associated gene. Exposure to Cre recombinase removes the floxed sequence - creating a null allele. These Fto^flox mice may be useful for in studying susceptibility to diet induced obesity, growth rate and metabolism, as well as anxiety-like behavior and impairments in working memory.

Of note, Fto knockout mice are distributed as B6.129(CBA)-Fto^tm1.2Pzg/J (Stock No. 034855).

Detailed description

The targeted Fto gene encodes a nuclear enzyme that is involved in obesity, glucose metabolism, energy homeostasis, and mRNA stability. Mutations in this gene have been associated with growth retardation, developmental delay, and facial dysmorphism (GDFD), and susceptibility to obesity.

These Fto^flox mice possess loxP sites on either side of exon 3 of the targeted gene. Mice that are homozygous for this allele are viable and fertile. When these mutant mice are bred to mice that express Cre recombinase, resulting offspring will have exon 3 deleted in the cre-expressing tissues. Removal of the floxed sequence creates a null allele.

When bred to a strain with Cre recombinase expression in early embryonic development (see Stock No. 003755 for example), this mutant mouse strain may be useful in studies of metabolism, growth and susceptibility to diet induced obesity.

Of note, Fto knockout mice are distributed as B6.129(CBA)-Fto^tm1.2Pzg/J (Stock No. 034855).

Development

A targeting vector was designed to insert a loxP site upstream of exon 3, and a frt-flanked PGK-EM7-Neo cassette followed by a loxP site just downstream of exon 3 of the fat mass and obesity associated locus (Fto) on chromosome 8. This construct was electroporated into 129P2/OlaHsd-derived E14TG2a.4 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. The resulting chimeric animals were crossed to mice (on the 129S4/SvJaeSor genetic background) expressing FLP1 recombinase (Stock No. 003946) to excise the selection cassette. Mice that retained the loxP site flanked exon 3 were then bred to C57BL/6 mice to remove the FLP1 recombinase allele. The resulting Fto^flox mice were then backcrossed to C57BL/6 for 4 generations. During backcrossing, the Y chromosome may not have been fixed to the C57BL/6J genetic background. Heterozygotes were crossed to generate homozygotes. Upon arrival at The Jackson Laboratory Repository, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J oocytes (Stock No. 000664).

Allele

Symbol: Fto^tm1.1Pzg
Name: targeted mutation 1.1, Pumin Zhang
MGI accession ID: MGI:4868738
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); No functional change
Synonyms: Fto^flox
Marker symbol: Fto
Marker name: fat mass and obesity associated
Marker synonyms: ALKBH9; BMIQ14; GDFD; IFEX9; mKIAA1752; RGD1305121
Chromosome: 8
Strain of origin: 129P2/OlaHsd
Molecular note: A loxP site was inserted upstream of exon 3, and an FRT-flanked neo cassette with a 5' loxP site was inserted dowstream of exon 3. Flp-mediated recombination removed the neo cassette leaving exon 3 floxed.