B6.129(CBA)-Fto^tm1.2Pzg/J

Stock number: 034855
Product name: Fto^#Δ
Research areas: Cell Biology Research, Developmental Biology Research, Diabetes and Obesity Research, Metabolism Research

Description

Fto^#Δ knockout mice have exon 3 deleted in the fat mass and obesity associated (Fto) gene. Homozygotes exhibit immediate growth retardation and 50% of homozygous mice die with in 2 weeks. These mice may be useful for studying susceptibility to diet induced obesity, growth rate and metabolism.

Of note, Fto conditional knockout mice (loxP-flanked exon 3) are distributed as B6.129-Fto^tm1.1Pzg/YxtJ (Stock No. 027830).

Detailed description

The targeted Fto gene encodes a nuclear enzyme that is involved in obesity, glucose metabolism, energy homeostasis, and mRNA stability. Mutations in this gene have been associated with growth retardation, developmental delay, facial dysmorphism (GDFD), and susceptibility to obesity. Fto^#Δ knockout mice have exon 3 removed by cre-mediated recombination. Exon 3 encodes 40% of the protein, and removal of exon 3 results in a frameshift and early termination in translation. Mice homozygous for Fto^#Δ are viable, however, only 50% of mice survive to postnatal day 10-14. Homozygotes develop immediate postnatal growth retardation, with shorter body length, lower body weight, decreased serum levels of IGF1 (insulin-like growth factor 1) and lower bone mineral density, although body composition is similar to wildtype. In addition, mice are susceptible to high-fat diet induced obesity and exhibit increased oxygen consumption and carbon dioxide production and increased food intake (relative to lean mass). Of note, 50% of mice on high fat diet develop dermatitis and become lean due to illness at the end of the 6 week diet regime. These mice may be useful for studying susceptibility to diet induced obesity, growth rate and metabolism.

Of note, Fto conditional knockout mice (loxP-flanked exon 3) are distributed as B6.129-Fto^tm1.1Pzg/YxtJ (Stock No. 027830).

Development

Mice from the B6.129-Fto^tm1.1Pzg/YxtJ (Stock No. 027830) colony were crossed to B6.Cg-Edil3^{Tg(Sox2-cre)1Amc}/J (Stock No. 008454) mice for germline deletion of the loxP-flanked exon 3. Deletion of exon 3, which encodes 40% of the protein, results in a frameshift of the downstream exons and early termination in translation. Western blot analysis confirmed the absence of protein in brain, white adipose, and brown adipose tissues. Progeny were interbred to generate homozygotes and the cre-expressing transgene was bred out of the colony.

A 48 SNP (single nucleotide polymorphism) panel analysis, with 43 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. Four of the 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating, including the rd8 recessive mutation associated with retinal degeneration on Chromosome 1 within the Crb1 locus. These data suggest the mice at The Jackson Laboratory Repository are on a mixed C57BL/6N;C57BL/6J genetic background.

Allele

Symbol: Fto^tm1.2Pzg
Name: targeted mutation 1.2, Pumin Zhang
MGI accession ID: MGI:4868744
Generation method: Targeted
Attributes: Null/Knockout
Synonyms: Fto^#delta
Marker symbol: Fto
Marker name: fat mass and obesity associated
Marker synonyms: ALKBH9; BMIQ14; GDFD; IFEX9; mKIAA1752; RGD1305121
Chromosome: 8
Strain of origin: 129P2/OlaHsd
Molecular note: Cre mediated recombination removed exon 3 from Fto^tm1.1Pzg. The absence of protein expression was confirmed by western blot analysis on brain, white adipose, and brown adipose extracts.