STOCK Foxo3^tm1Rdp/J

Stock number: 024668
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.

Of note, the same Foxo3^L/L floxed allele is also available on a C57BL/6J genetic background as Stock No. 037528.

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.

Of note, the same Foxo3^L/L floxed allele is also available on a C57BL/6J genetic background as Stock No. 037528.

Development

A targeting vector was designed to insert a loxP site, followed by a 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 donating investigator reported that mice were bred to FVB mice for at least 3 generations before being bred with mice carrying Foxo4^tm1Rdp and Foxo1^tm1Rdp (see SNP note below). Upon arrival, mice were bred to FVB/NJ inbred mice (Stock No. 001800) for at least one generation to establish the colony. The three alleles in this strain were separated and maintained as separate strains (for Foxo4^tm1Rdp see Stock No. 024757 and for Foxo1^tm1Rdp see Stock No. 024756). Single mutants were bred to FVB/NJ for at least one more generation.

A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. Three of the 27 markers throughout the genome were segregating, suggesting an incomplete backcross.

Allele

Symbol: Foxo3^tm1Rdp
Name: targeted mutation 1, Ronald DePinho
MGI accession ID: MGI:2668317
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); No functional change
Synonyms: Foxo3^f; FoxO3^L
Marker symbol: Foxo3
Marker name: forkhead box O3
Marker synonyms: 1110048B16Rik; 2010203A17Rik; AF6q21; Fkhr2; Fkhrl1; FKHRL1P1; FKHRL1P2; FOXO2; Foxo3a; ZNF286C
Chromosome: 10
Strain of origin: 129S6/SvEvTac
Molecular note: Exon 2, which is the first coding exon, was flanked by a loxP-frt-neo-frt cassette in intron 1 and single loxP site in intron 2. Mice carrying this allele were bred with cre transgenic mice to generate Foxo3^tm1.1Rdp.
General note:

Phenotypic Similarity to Human Syndrome: Granulosa Cell Tumor of the ovary J:232961.