B6.129S6(Cg)-Foxo3^tm1.2Rdp/JussJ

Stock number: 037528
Product name: FoxO3^L
Strain synonyms: Foxo3^f
Research areas: Apoptosis Research, Cell Biology Research, Research Tools

Description

FoxO3^L/L floxed mice may be useful for studying the regulatory role of the FOXO3 transcription factor on cell survival and tumor suppression.

Stock No. 037528 is a C57BL/6J-congenic FoxO3^L/L floxed mouse line. Of note, the same FoxO3^L/L floxed allele is also available on a mixed genetic background as Stock No. 024668.

Detailed description

These FoxO3^L/L mutant mice possess loxP sites flanking exon 2 of the forkhead box O3 (Foxo3) gene. FOXO3 is a transcription factor which regulates the expression of genes involved in stress resistance, cell cycle progression, tumor progression, longevity, autophagy, and apoptosis. FOXO3 has also been shown to be a tumor suppressor. Mice that are homozygous for this allele are viable and fertile. When these mutant mice are bred to mice that express Cre recombinase, the resulting offspring will have exon 2 deleted in the cre-expressing tissue, resulting in inactivation of Foxo3 gene expression.

In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. It should be noted that the phenotype of these C57BL/6J-congenic mice could vary from that originally described on a mixed genetic background. We may modify the strain description if necessary, as published results become available.

Development

A targeting vector was designed by Dr. Ronald DePinho, to insert a loxP site, followed by an FRT-flanked neomycin resistance (neo) cassette upstream of exon 2, and a single loxP site downstream of exon 2 of the forkhead box O3 (Foxo3) gene. The construct was electroporated into 129S6/SvEvTac-derived TC1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and resulting chimeric mice were bred to FVB/N mice to establish a colony. The subsequent progeny were backcrossed to FVB mice for at least 3 generations prior to arriving at The Jackson Laboratory as Stock No. 024668.

Dr. John Ussher purchased some Stock No. 024668 animals, on the mixed genetic background and crossed these to Flp transgenic mice (Stock No. 005703) to remove the neo cassette. The resulting FoxO3^L/+ mice, with neo cassette removed and floxed exon 2 intact, were then backcrossed at least 6 generations to C57BL/6J inbred mice (Stock No. 000664) before sending mice back to The Jackson Laboratory. The resulting C57BL/6J-congenic strain is called B6(Cg)-Foxo3^tm1.2Rdp/JussJ. Upon arrival at The Jackson Laboratory, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J oocytes.

Allele

Symbol: Foxo3^tm1.2Rdp
Name: targeted mutation 1.2, Ronald DePinho
MGI accession ID: MGI:7310460
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed)
Synonyms: FoxO3^L
Marker symbol: Foxo3
Marker name: forkhead box O3
Marker synonyms: 1110048B16Rik; 2010203A17Rik; AF6q21; Fkhr2; Fkhrl1; FKHRL1P2; FOXO2; Foxo3a
Chromosome: 10
Strain of origin: 129S6/SvEvTac
Molecular note: The targeting vector is designed to insert a loxP site, followed by an FRT-flanked neomycin resistance (neo) cassette upstream of exon 2, and a single loxP site downstream of exon 2. Flp-mediated recombination removed the neomycin cassette.