B6.129Sv(Cg)-Fgf21^tm1.1Djm/J

Stock number: 033846
Product name: Fgf21 KO
Research areas: Diabetes and Obesity Research, Metabolism Research

Description

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.

Detailed description

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.

Development

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 Fgf21^loxP 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 Fgf21^loxP 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

Symbol: Fgf21^tm1.1Djm
Name: targeted mutation 1.1, David J Mangelsdorf
MGI accession ID: MGI:4354163
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Fgf21
Marker name: fibroblast growth factor 21
Marker synonyms: Fgf8c
Chromosome: 7
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.