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Journal of Lipid Research, Vol. 50, 1870-1880, September 2009
Copyright © 2009 by American Society for Biochemistry and Molecular Biology

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 and Manabu T. Nakamura^1,*,

^* Division of Nutritional Sciences, Department of Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, Urbana, IL 61801
Department of Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, Urbana, IL 61801
Department of Pathobiology, University of Illinois at Urbana-Champaign, Urbana, IL 61801
^** Department of Veterinary Biosciences, University of Illinois at Urbana-Champaign, Urbana, IL 61801
Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853

¹ To whom correspondence should be addressed. e-mail: mtnakamu{at}illinois.edu

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-¹³C]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.—Stroud, C. K., T. Y. Nara, M. Roqueta-Rivera, E. C. Radlowski, P. Lawrence, Y. Zhang, B. H. Cho, M. Segre, R. A. Hess, J. T. Brenna, W. M. Haschek, and M. T. Nakamura. Disruption of FADS2 gene in mice impairs male reproduction and causes dermal and intestinal ulceration.

Supplementary key words arachidonic acid • delta-6 desaturase • docosahexaenoic acid • docosapentaenoic acid • eicosanoid • essential fatty acid • FADS3 • prostaglandin

Abbreviations: AA, arachidonic acid; ALA, alpha-linolenic acid; D5D, delta-5 desaturase; D6D, delta-6 desaturase; DHA, docosahexaenoic acid; DPA n-6, docosapentaenoic acid (n-6); HUFA, highly unsaturated fatty acid; LA, linoleic acid; PG, prostaglandin

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