title: The iFat1 transgene permits conditional endogenous n-3 PUFA enrichment both in vitro and in vivo.
abstract: Fat-1 transgenic mice, which endogenously convert n-6 PUFA to n-3 PUFA, are a useful tool in health research; however with this model timing of n-3 PUFA enrichment cannot be directly controlled. To add such capability, the novel Cre-recombinase inducible fat-1 (iFat1) transgenic mouse has been developed. The aim of this study was to characterize the utility of the iFat1 transgene as a model of Cre-inducible endogenous n-3 PUFA enrichment. Functionality of the iFat1 transgene was screened both in vitro and in vivo. In the presence of Cre, the iFat1 transgene resulted in a balancing (p < 0.01) of the n-6/n-3 PUFA ratio within phospholipids in the human embryonic kidney 293T cell line. For in vivo analysis, iFat1 transgenic mice were crossed with the R26-Cre-ER(T2) (Tam-Cre) mouse line, a tamoxifen inducible Cre-expression model. Tam-Cre/iFat1 double hybrids were transiently treated with tamoxifen at 6-7 weeks, then terminated 3 weeks later. Tamoxifen treated mice had increased (p < 0.05) tissue n-3 PUFA and ≥two-fold reduction (p < 0.05) in the n-6/n-3 PUFA ratio of liver, kidney and muscle phospholipids relative to vehicle treated controls. Collectively these findings suggest that the iFat1 transgenic mouse may be a promising tool to help elucidate the temporal effects through which n-3 PUFA impacts health related outcomes.
authors.affiliation: Department of Human Health and Nutritional Sciences, University of Guelph, 50 Stone Road East, Guelph, ON, N1G 2W1, Canada.
authors.forename: Shannon E
authors.initials: SE
authors.lastname: Clarke
authors.forename: Jing X
authors.initials: JX
authors.lastname: Kang
authors.forename: David W L
authors.initials: DW
authors.lastname: Ma
mesh_terms: D000818:Animals; D015820:Cadherins / Q000096:biosynthesis / Q000235:genetics*; D015525:Fatty Acids, Omega-3 / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D066298:In Vitro Techniques; D019426:Integrases / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic
chemical_list: D015820:Cadherins; D015525:Fatty Acids, Omega-3; C502406:fat1 protein, mouse; C045073:Cre recombinase; D019426:Integrases