|FGF21 transgenic mice have the apolipoprotein E (ApoE) promoter/enhancer sequences driving expression of fibroblast growth factor 21 (Fgf21). These mice may be useful for studying the role of FGF21 in coordinating metabolic responses to fasting.|
Type Coisogenic; Mutant Strain; Transgenic; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse Donating Investigator Steven A Kliewer, UTSouthwestern Medical Center
FGF21 transgenic mice have the murine apolipoprotein E (ApoE) promoter/enhancer sequences driving expression of fibroblast growth factor 21 (Fgf21) in liver. Mice from founder line 1, containing a 50 fold increase in Fgf21 mRNA levels over fasted wildtype mice, were established. FGF21 is an endocrine hormone, expressed in liver, pancreas, and adipose tissue, which stimulates glucose uptake in adipocytes. FGF21 is induced by peroxisome proliferator-activated receptor a (PPARa) in liver during fasting and induces hepatic fatty acid oxidation and ketogenesis. Hemizygotes are viable, with only male transgenic mice are fertile. Overexpression of FGF21 extends the life span of these FGF21 transgenic mice. They have significant reductions in serum cholesterol, glucose, and insulin. In the liver, they have increased oxygen consumption, beta oxidation, gluconeogenesis, and glycogen content. They have decreased serum and hepatic triglyceride concentrations. In these mice, mRNAs encoding pancreatic lipases are increased in liver and adipocyte size is decrease. These mice are more sensitive to torpor during a 24 hour fast.
The FGF21 transgene was designed with a murine fibroblast growth factor 21 (Fgf21) cDNA driven by murine apolipoprotein E (ApoE) promoter/enhancer sequences. The transgene was microinjected into fertilized C57BL/6NCrl oocytes and mice from founder line 1 were bred to C57BL/6J mice to establish a colony. These mice were bred to C57BL/6J mice for at least ten generations. Upon arrival at The Jackson Laboratory, transgenic mice were bred to C57BL/6J inbred mice (Stock No. 000664) for one generation.
|Wild-type from the colony|
|Considerations for Choosing Controls|
Strains carrying other alleles of Apoe
014556 129S6/SvEv-Apoetm4Mae/J 002246 B6.129-Apoetm1Unc Ldlrtm1Her/J 002052 B6.129P2-Apoetm1Unc/J 013040 B6.Cg-Apoetm1Unc Ins2Akita/J 007224 B6.Cg-Apoetm1Unc (D12Mit182-D12Mit2)/Pgn 008525 B6.Cg-Tg(Cyp21a1-Apoe)619Fet/J 004632 B6.Cg-Tg(GFAP-APOE_i2)14Hol Apoetm1Unc/J 004633 B6.Cg-Tg(GFAP-APOE_i3)37Hol Apoetm1Unc/J 004631 B6.Cg-Tg(GFAP-APOE_i4)1Hol Apoetm1Unc/J 002878 B6;129-Apobtm1Sgy Apoetm1Unc/J 002879 B6;129-Apobtm2Sgy Apoetm1Unc/J 002245 B6;129-Apoetm1Unc Ldlrtm1Her/J 004362 B6;129-Scarb1tm1Kri Apoetm1Unc/J 007067 D2.129P2(B6)-Apoetm1Unc/J 013719 D2.Cg-Apoetm1Unc Ins2Akita/J 007069 STOCK Apoetm1Unc/JView Strains carrying other alleles of Apoe (16 strains)Strains carrying other alleles of Fgf21View Strains carrying other alleles of Fgf21 (1 strain)
View Mammalian Phenotype TermsMammalian Phenotype Terms provided by MGIassigned by genotype
The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.
Tg(Apoe-Fgf21)1Sakl/0Background Not Specified
- homeostasis/metabolism phenotype
- abnormal gluconeogenesis
- increased glycogen level
- liver glycogen content increased 50% compared to in wild-type mice (MGI Ref ID J:150831)
- increased oxygen consumptionView Research ApplicationsResearch ApplicationsThis mouse can be used to support research in many areas including:
Developmental Biology Research
Diabetes and Obesity Research
Endocrine Deficiency Research
exocrine pancreatic insufficiency
Low Body Temperature
|Allele Name||transgene insertion 1, Steven A Kliewer|
|Allele Type||Transgenic (random, expressed)|
|Strain of Origin||C57BL/6NCrl|
|Expressed Gene||Fgf21, fibroblast growth factor 21, mouse, laboratory|
|Promoter||Apoe, apolipoprotein E, mouse, laboratory|
|Molecular Note||The mouse promoter was used to drive liver-specific expression of the mouse cDNA. Two lines were created (1 and 2) that result in 50-fold, and 150-fold, respectively, higher expression of the transcript compared to in wild-type mice. The two lines exhibit virtually identical changes in fasting serum beta-hydroxybutyrate, triglyceride, total cholesterol, glucose, and insulin concentrations. Line 1 was selected as the representative line. [MGI Ref ID J:129855]|
Inagaki T; Dutchak P; Zhao G; Ding X; Gautron L; Parameswara V; Li Y; Goetz R; Mohammadi M; Esser V; Elmquist JK; Gerard RD; Burgess SC; Hammer RE; Mangelsdorf DJ; Kliewer SA. 2007. Endocrine Regulation of the Fasting Response by PPARalpha-Mediated Induction of Fibroblast Growth Factor 21. Cell Metab 5(6):415-25. [PubMed: 17550777] [MGI Ref ID J:129855]
Bookout AL; de Groot MH; Owen BM; Lee S; Gautron L; Lawrence HL; Ding X; Elmquist JK; Takahashi JS; Mangelsdorf DJ; Kliewer SA. 2013. FGF21 regulates metabolism and circadian behavior by acting on the nervous system. Nat Med 19(9):1147-52. [PubMed: 23933984] [MGI Ref ID J:201888]
Ding X; Boney-Montoya J; Owen BM; Bookout AL; Coate KC; Mangelsdorf DJ; Kliewer SA. 2012. betaKlotho is required for fibroblast growth factor 21 effects on growth and metabolism. Cell Metab 16(3):387-93. [PubMed: 22958921] [MGI Ref ID J:189018]
Pashkov V; Huang J; Parameswara VK; Kedzierski W; Kurrasch DM; Tall GG; Esser V; Gerard RD; Uyeda K; Towle HC; Wilkie TM. 2011. Regulator of G Protein Signaling (RGS16) Inhibits Hepatic Fatty Acid Oxidation in a Carbohydrate Response Element-binding Protein (ChREBP)-dependent Manner. J Biol Chem 286(17):15116-25. [PubMed: 21357625] [MGI Ref ID J:172091]
Potthoff MJ; Inagaki T; Satapati S; Ding X; He T; Goetz R; Mohammadi M; Finck BN; Mangelsdorf DJ; Kliewer SA; Burgess SC. 2009. FGF21 induces PGC-1alpha and regulates carbohydrate and fatty acid metabolism during the adaptive starvation response. Proc Natl Acad Sci U S A 106(26):10853-8. [PubMed: 19541642] [MGI Ref ID J:150831]
Wei W; Dutchak PA; Wang X; Ding X; Wang X; Bookout AL; Goetz R; Mohammadi M; Gerard RD; Dechow PC; Mangelsdorf DJ; Kliewer SA; Wan Y. 2012. Fibroblast growth factor 21 promotes bone loss by potentiating the effects of peroxisome proliferator-activated receptor gamma. Proc Natl Acad Sci U S A 109(8):3143-8. [PubMed: 22315431] [MGI Ref ID J:182005]
Zhang Y; Xie Y; Berglund ED; Coate KC; He TT; Katafuchi T; Xiao G; Potthoff MJ; Wei W; Wan Y; Yu RT; Evans RM; Kliewer SA; Mangelsdorf DJ. 2012. The starvation hormone, fibroblast growth factor-21, extends lifespan in mice. Elife 1:e00065. [PubMed: 23066506] [MGI Ref ID J:197581]
Breeding & Husbandry Hemizygous females are infertile. When maintaining a live colony, wildtype (noncarrier) females from the colony or C57BL/6J females may be bred with hemizygous males.
This strain is currently Awaiting Transfer from the Donor.This strain is not yet on campus, but was accepted to be imported to the JAX® Repository on 08-MAY-13. View All Strains Awaiting Transfer from the Donor, In Progress and On Hold
|Wild-type from the colony|
|Considerations for Choosing Controls|
|Control Pricing Information for Genetically Engineered Mutant Strains.|
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