Disruption of FADS2 gene in mice impairs male reproduction and causes dermal and intestinal ulceration

Chad K. Stroud, Takayuki Y. Nara, Manuel Roqueta-Rivera, Emily C. Radlowski, Peter Lawrence, Ying Zhang, Byung H. Cho, Mariangela Segre, Rex A. Hess, J. Thomas Brenna, Wanda M. Haschek, Manabu T. Nakamura

Research output: Contribution to journalArticlepeer-review


Delta-6 desaturase (D6D) catalyzes the first step in the synthesis of highly unsaturated fatty acids (HUFA) such as arachidonic (AA), docosapentaenoic (DPAn-6), and docosahexaenoic (DHA) acids, as well as the last desaturation of DPAn-6 and DHA. We created D6D-null mice (-/-), which enabled us to study HUFA deficiency without depleting their precursors. In -/-, no in vivo AA synthesis was detected after administration of [U-13 C]linoleic acid (LA), indicating absence of D6D isozyme. Unexpectedly, all of the -/- developed ulcerative dermatitis when fed a purified diet lacking D6D products but containing ample LA. The -/- also exhibited splenomegaly and ulceration in duodenum and ileocecal junction. Male -/- lacked normal spermatozoa with a severe impairment of spermiogenesis. Tissue HUFAs in -/- declined differentially: liver AA and DHA by 95%, and a smaller decrease in brain and testes. Dietary AA completely prevented dermatitis and intestinal ulcers in -/-. DPAn-6 was absent in -/- brain under AA supplementation, indicating absence of D6D isozyme for DPAn-6 synthesis from AA. This study demonstrated a distinct advantage of the D6D-null mice (-/-) to elucidate (1) AA function without complication of LA deprivation and (2) DHA function in the nervous system without AA depletion or DPAn-6 replacement seen in traditional models.

Original languageEnglish (US)
Pages (from-to)1870-1880
Number of pages11
JournalJournal of Lipid Research
Issue number9
StatePublished - 2009


  • Arachidonic acid
  • Delta-6 desaturase
  • Docosahexaenoic acid
  • Docosapentaenoic acid
  • Eicosanoid
  • Essential fatty acid
  • FADS3
  • Prostaglandin

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology


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