Delta6-desaturase (FADS2) deficiency unveils the role of omega3- and omega6-polyunsaturated fatty acids.
Mammalian cell viability is dependent on the supply of the essential fatty acids (EFAs) linoleic and alpha-linolenic acid. EFAs are converted into omega3- and omega6-polyunsaturated fatty acids (PUFAs), which are essential constituents of membrane phospholipids and precursors of eicosanoids, anandamide and docosanoids. Whether EFAs, PUFAs and eicosanoids are essential for cell viability has remained elusive. Here, we show that deletion of delta6-fatty acid desaturase (FADS2) gene expression in the mouse abolishes the initial step in the enzymatic cascade of PUFA synthesis. The lack of PUFAs and eicosanoids does not impair the normal viability and lifespan of male and female fads2 -/- mice, but causes sterility. We further provide the molecular evidence for a pivotal role of PUFA-substituted membrane phospholipids in Sertoli cell polarity and blood-testis barrier, and the gap junction network between granulosa cells of ovarian follicles. The fads2 -/- mouse is an auxotrophic mutant. It is anticipated that FADS2 will become a major focus in membrane, haemostasis, inflammation and atherosclerosis research.
Stoffel
Wilhelm
W
Center of Molecular Medicine (CMMC), Laboratory of Molecular Neurosciences, Institute of Biochemistry, University of Cologne, Cologne, Germany. wilhelm.stoffel@uni-koeln.de
Holz
Barbara
B
Jenke
Britta
B
Binczek
Erika
E
Günter
Robert Heinz
RH
Kiss
Christine
C
Karakesisoglou
Iakowos
I
Thevis
Mario
M
Weber
Artur-Aron
AA
Arnhold
Stephan
S
Addicks
Klaus
K
D000818:Animals; D001814:Blood-Testis Barrier / Q000502:physiology; D050260:Carbohydrate Metabolism; D016764:Cell Polarity / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D015777:Eicosanoids / Q000096:biosynthesis; D015525:Fatty Acids, Omega-3 / Q000378:metabolism*; D043371:Fatty Acids, Omega-6 / Q000378:metabolism*; D005260:Female; D007246:Infertility / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D050602:Linoleoyl-CoA Desaturase / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D050356:Lipid Metabolism; D008264:Macrophages / Q000201:enzymology / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D006080:Ovarian Follicle / Q000502:physiology; D012708:Sertoli Cells / Q000378:metabolism / Q000473:pathology; D013923:Thromboembolism / Q000201:enzymology / Q000235:genetics / Q000517:prevention & control
D015777:Eicosanoids; D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D050602:Linoleoyl-CoA Desaturase