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  • The EMBO Journal (2008) 27, 2281 - 2292
  • doi:10.1038/emboj.2008.156

Published online: 7 August 2008

Delta6-Desaturase (FADS2) deficiency unveils the role of omega3- and omega6-polyunsaturated fatty acids

Wilhelm Stoffel1, Barbara Holz1, Britta Jenke1, Erika Binczek1, Robert Heinz Günter1, Christine Kiss1, Iakowos Karakesisoglou1, Mario Thevis2, Artur-Aron Weber3, Stephan Arnhold4 and Klaus Addicks4

  1. Center of Molecular Medicine (CMMC), Laboratory of Molecular Neurosciences, Institute of Biochemistry, University of Cologne, Cologne, Germany
  2. Institute of Biochemistry, DSHS Cologne, Cologne, Germany
  3. Department of Pharmacology, Universitätsklinikum Essen, Essen, Germany
  4. Department of Anatomy I, University of Cologne, Cologne, Germany

Correspondence to:

Wilhelm Stoffel, Center of Molecular Medicine (CMMC), Laboratory of Molecular Neurosciences, Institute of Biochemistry, University of Cologne, Joseph-Stelzmann-Strabetae 52, 50931 Cologne, Germany. Tel.: +49 221 478 6881; Fax: +49 221 478 6882; E-mail: wilhelm.stoffel@uni-koeln.de

Received 20 February 2008; Accepted 17 July 2008

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.

  • Keywords:

    • Delta6 fatty acid desaturase deficiency,
    • eicosanoid deficiency,
    • essential fatty acids,
    • lack of PUFA synthesis,
    • male and female sterility