Fatty acid desaturase 3 null mouse biochemical phenotype (246.5)

Abstract

Introduction. We report here generation of the first Fads3 knockout (KO) mouse and initial observations about its biochemical phenotype. Fatty acid desaturase 3 (FADS3) is a member of the FADS gene cluster. FADS1 and FASDS2 code for the rate‐limiting enzymes in LCPUFA biosynthesis. FADS3 has no known function.Methods. All mice (wild type (WT) and KO) were fed standard rodent chow devoid of LCPUFA. Brain and livers were harvested on day 1, 3, 7, 13, 21, and 30 of age for fatty acid and gene expression analysis. Gene expression levels were measured by quantitative and semi‐quantitative real time PCR.Preliminary Results. No differences in overt phenotypes (survival, fertility, growth rate) were observed between WT and KO. Docosahexaenoic acid (DHA, 22:6n‐3) levels in the brain of postnatal day 1 (P1) KO mice were significantly (P<0.05) lower than the WT. No significant Fads1 and Fads2 mRNA expression changes were detected. Elovl2 is known to catalyze the conversion of C20 PUFA. Hepatic Elovl2 expression was significantly upregulated in P1 KO mice compared to WT, and the 22:6n‐3‐precursor 22:5n‐3 was about double in KO vs WT mice.Conclusion. Fads3 null mice have lower brain 22:6n‐3, greater liver 22:5n‐3, and greater liver Elovl2 expression on Day1, though all levels normalize within days. Fads3 appears to influence liver‐mediated 22:6n‐3 synthesis and brain 22:6n‐3 accretion in perinatal life in the Fads3 KO mouse.Grant Funding Source: NIH R01 AT007003