Fgf21 knock-out mice lack exons 1-3 of the fibroblast growth factor 21 (Fgf21) gene. These mice may be useful for studying the role of FGF21 in coordinating metabolic responses to fasting.
David Mangelsdorf, UT Southwestern Medical Center
Fgf21 knock-out mice lack exons 1-3 of the fibroblast growth factor 21 (Fgf21) gene. FGF21 is an endocrine hormone, expressed in liver and pancreas, which stimulates glucose uptake in adipocytes. FGF21 induction in liver by peroxisome proliferator-activated receptor a (PPARa) during fasting induces fatty acid oxidation ketogenesis in liver. Homozygotes are viable and fertile. Livers from these mice have decreased beta-oxidation, ketogenesis, and gluconeogenesis under fasted conditions.
Of note, the floxed version of this allele is available as Stock No. 022361.
A targeting vector was designed to insert a loxP site upstream of exon 1, followed by a second loxP site and a frt-flanked neomycin resistance (neo) cassette downstream of exon 3 of the fibroblast growth factor 21 (Fgf21) gene. The construct was electroporated into 129S6/SvEvTac embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts and resulting chimeric males were bred to C57BL/6J females. Offspring were bred with B6;SJL-Tg(ACTFLPe)9205Dym/J transgenic mice (Stock No. 003800) to delete the neo cassette, and progeny were crossed to remove the Flp-expressing transgene. The resulting Fgf21loxP mice were bred to C57BL/6 mice for at least 10 generations. Upon arrival, mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the Fgf21loxP colony as Stock No. 022361. Subsequently, some of the floxed mice were further crossed to Sox2-cre mice (Stock No. 008454) to remove the floxed exons 1-3, creating this Fgf21 knock-out strain.
|Allele Name||targeted mutation 1.1, David J Mangelsdorf|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Fgf21, fibroblast growth factor 21|
|Strain of Origin||129S6/SvEvTac|
|Molecular Note||Germline, cre mediated recombination removed exons 1 through 3. The absence of transcript expression was confirmed by RT-PCR or QPCR on liver extracts. The absence of plasma Fgf21 concentrations in fasted mice confirmed the lack of protein expression.|
When maintaining a live colony, homozygous mice may be bred together.
When using the Fgf21 KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #033846 in your Materials and Methods section.