Foxo1L/L floxed mice may be useful for studying the regulatory role of the FOXO1 transcription factor on insulin signaling, glucose production and tumor suppression.
Dr. Ronald DePinho, MD Anderson Cancer Center
These Foxo1L/L mutant mice possess loxP sites flanking exon 2 of the forkhead box O1 (Foxo1) gene. FOXO1 is a transcription factor which mediates the transcription of glucose-6-phosphatase, leading to gluconeogenesis and adipogenesis. FOXO1 is involved in the regulation of insulin signaling and metabolic homeostasis, and has 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 Foxo1 gene expression.
A targeting vector was designed to insert a loxP site upstream of exon 2, and a frt-flanked neomycin resistance (neo) cassette followed by a second loxP site downstream of exon 2 of the forkhead box O1 (Foxo1) 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 Tg(ACTFLPe)9205Dym transgenic mice to delete the neo cassette. Progeny were crossed to remove the Flp-expressing transgene. Mice were bred to FVB mice for at least 3 generations before being bred with mice carrying Foxo4tm1Rdp and Foxo3tm1Rdp. 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 Foxo4tm1Rdp see Stock No. 024757 and for Foxo3tm1Rdp see Stock No. 024668). Single mutants were bred to FVB/NJ for at least one more generation (see SNP note below).
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 still segregating, this suggests an incomplete backcross.
|Allele Name||targeted mutation 1, Ronald DePinho|
|Allele Type||Targeted (Conditional ready (e.g. floxed), No functional change)|
|Allele Synonym(s)||Fox1loxP; Foxo1F; Foxo1fl; FoxO1flox; FoxO1L|
|Gene Symbol and Name||Foxo1, forkhead box O1|
|Strain of Origin||129S6/SvEvTac|
|General Note|| |
Phenotypic Similarity to Human Syndrome: Granulosa Cell Tumor of the ovary J:232961.
|Molecular Note||Exon 2 was flanked with loxP sites. This exon is the first coding exon and contains the C-terminal half of the full-length protein.|
When maintaining a live colony, homozygous mice may be bred together.
When using the FoxO1L mouse strain in a publication, please cite the originating article(s) and include JAX stock #024756 in your Materials and Methods section.