B6;129-Gt(ROSA)26Sor^{tm1(Foxo1/GFP)Jke}/J

Stock number: 016262
Research areas: Cell Biology Research, Diabetes and Obesity Research, Research Tools

Description

The FOXO1/GFP allele contains a loxP-flanked transcriptional STOP cassette (PGK-Neo-polyA) upstream of a forkhead box O1 (Foxo1)-green fluorescent protein (GFP) fusion protein. These mice may be useful for generating conditional mutations for studying the role of PI3K-AKT signaling pathway on insulin resistance, glucose intolerance, diabetes, and aging.

Detailed description

The FOXO1/GFP allele contains a loxP-flanked transcriptional STOP cassette (PGK-Neo-polyA) upstream of a forkhead box O1 (Foxo1)-green fluorescent protein (GFP) fusion protein. Homozygotes are viable and fertile. In the absence of Cre, reporter gene expression is prevented by the STOP sequence. When bred to mice that express Cre recombinase, offspring will have the floxed-STOP cassette deleted in the cre-expressing tissue(s), resulting in FOXO1/GFP expression in Cre-recombinase-expressing cells. FOXO1 is a component of the phosphoinositide 3-kinase (PI3K)-AKT pathway, and shuttles between the nucleus and the cytoplasm upon activation/inhibition by AKT. The PI3K-AKT signaling pathway is activated after administration of insulin and leptin. Exclusion of FoxO1 from the nucleus upon AKT phosphorylation allows visualization of activated/inactivated AKT by monitoring sub-cellular localization of the FOXO1-GFP fusion protein. These mice may be useful for generating conditional mutations for studying the role of PI3K-AKT signaling pathway on insulin resistance, glucose intolerance, diabetes, and aging.

Development

The FOXO1/GFP targeting vector was designed with a loxP-flanked transcriptional STOP cassette (PGK-Neo-polyA) upstream of a forkhead box O1 (Foxo1)-green fluorescent protein (GFP) fusion protein. This vector was inserted into the Gt(ROSA)26Sor locus and was electroporated into 129-derived embryonic stem (ES) cells. The resulting chimeric mice were bred to C57BL/6J mice. Upon arrival at The Jackson Laboratory, mutant mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the colony.

Allele

Symbol: Gt(ROSA)26Sor^{tm1(Foxo1/GFP)Jke}
Name: targeted mutation 1, Joel K Elmquist
MGI accession ID: MGI:3830706
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); Reporter
Marker symbol: Gt(ROSA)26Sor
Marker name: gene trap ROSA 26, Philippe Soriano
Chromosome: 6
Strain of origin: 129
Expressed genes: Foxo1,forkhead box O1,mouse, laboratory; GFP,Green Fluorescent Protein,
Site of expression: When bred to mice that express Cre recombinase, the FOXO1-GFP fusion protein will be expressed in cells where promoters driving Cre recombinase are expressed.
Molecular note: A floxed neo-STOP cassette followed by a Foxo1/GFP fusion was inserted into the locus. Expression of the reporter construct can only be achieved by cre-mediated removal of the neo-STOP cassette.