B6;C3H-Tg(CAG-fat-2)1Jxk/J

Stock number: 034647
Product name: fat-2
Research areas: Cancer Research, Immunology, Inflammation and Autoimmunity Research, Metabolism Research, Research Tools

Description

FAT-2 transgenic mice are able to convert monounsaturated fatty acids to omega-6 (n-6) polyunsaturated fatty acids, increasing tissue levels of n-6 without special dietary adjustment, and may be useful in understanding the role of polyunsaturated fatty acids in chronic diseases.

Detailed description

The Caenorhabditis elegans fat-2 gene encodes an enzyme that endogenously converts monounsaturated fatty acids to omega-6 (n-6) polyunsaturated fatty acids (PUFA). These FAT-2 mice express a (codon modified) Caenorhabditis elegans fat-2 gene, under the control of the CAG, CMV-IE enhancer/chicken beta-actin/rabbit beta-globin hybrid promoter with widespread expression. FAT-2 mice have increased tissue levels of n-6 PUFA and a high tissue ratio of n-6/n-3 PUFA. In comparison to Western diet-fed FAT-1 mice or FAT-1+2 mice, FAT-2 mice fed Western diet (modified AIN-76A 40% fat) for 16 months have higher body weights, expend less energy, develop larger and increased numbers of adipocytes, have reduced glucose tolerance, increased lipid accumulation, fatty liver, liver tumors (86% of 16 month old mice), increases in inflammatory markers, and altered gut microbiota (as well as fecal and serum metabolite) composition.

The donating investigator indicates that FAT-2 homozygotes are viable and fertile. This strain may be useful in understanding the role of polyunsaturated fatty acids in chronic diseases.

Of note, the FAT-1 strain (C57BL/6-Tg(CAG-fat-1)1Jxk/J) is available as Stock No. 020097.

Combining FAT-2 and FAT-1 mice (also called Omega mice) allows manipulation of tissue n-6/n-3 PUFA ratios, which can alter the gut microbiome, fecal and serum metabolites and change risk for metabolic diseases and cancer.

Development

A transgenic construct containing Caenorhabditis elegans fat-1 sequence (with modification of codon usage for mammalian cells) under the control of the CAG, CMV-IE enhancer/chicken beta-actin/rabbit beta-globin hybrid promoter, was injected into fertilized C57BL/6 X C3H mouse eggs. Founder line 1 was subsequently established and bred to C57BL/6. The strain was maintained on a mixed background. Upon arrival, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J oocytes (Stock No. 000664).

Allele

Symbol: Tg(CAG-fat-2)1Jxk
Name: transgene insertion 1, Jing X Kang
MGI accession ID: MGI:6356859
Generation method: Transgenic
Attributes: Inserted expressed sequence
Marker symbol: Tg(CAG-fat-2)1Jxk
Marker name: transgene insertion 1, Jing X Kang
Chromosome: UN
Strain of origin: C57BL/6 x C3H
Site of expression: widespread pattern of expression
Molecular note: The C. elegans fat-2 gene was modified to optimize codon usage for mammalian cells and was expressed in mice under the control of a chicken beta-actin promoter (pCAGGS, which allows high-level and broad expression of the transgene in mice).