The lack of polyunsaturated fatty acids (PUFAs) in the fads2-/- mouse abolishes the precursor of eicosanoid synthesis in the cyclic (cyclooxygenases) and linear (lipoxygenase) pathways. FADS-2 deficiency disturbs the initial platelet aggregation step in the coagulation system. PUFA deficiency in phospholipids of the membrane lipid bilayer has a strong impact on membrane domain structures, e.g. leads to the disruption of intercellular adherens junction systems of the blood-testis barrier and causes male and female sterility. This barrier function defect together with male and female infertility can be restored specifically by dietary supplementation with ?3-docosahexaenoic acid. The many facets of the complex phenotype of the auxotrophic fads2-/- mutant are currently under investigation.
Biosynthetic pathways: from dietary ω3 (?18:3) and ω6 (18:2) essential fatty acids to ω3 and ω6 polyunsaturated fatty acids.
Sections of testis and epidiymis of wt and fads2-/- mice. Wt testis showed normal spermatogenesis and wt epididymis tubular system showed mature spermatozoa in the lumen of the seminiferous tubuli.
Induction of vascular injury and thrombosis in carotid artery (cross sections of carotid arteries). Thrombotic obliteration of the carotid artery of wt (+/+) mice and resistance to thrombosis in fads2-/- mice.
Literature
ß-Oxidation of polyunsaturated fatty acids: mechanism of mitochondrial 3,2-trans-enoyl-CoA isomerase
U. Jansen, W. Stoffel (2002) Disruption of mitochondrial ß-oxidation of unsaturated fatty acids in the 3, 2trans-enoyl-CoA isomerase deficient mouse J. Biol. Chem. 277, 19579-19584
U. Janssen, E. Davies, M.M. LeBeau, W. Stoffel (1997) Human mitochondrial enoyl.-CoA hydratase gene (ECHS1): Structural organization and assignment to chromosome 10q26.2-q26.3 Genomics 40, 470-475
From bench to bedside: Refsum Syndrom