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

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

Journal of lipid research, 2009-09, Vol.50 (9), p.1870-1880 [Periódico revisado por pares]

United States: Elsevier Inc

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Título:
Disruption of FADS2 gene in mice impairs male reproduction and causes dermal and intestinal ulceration
Autor: Stroud, Chad K. ; Nara, Takayuki Y. ; Roqueta-Rivera, Manuel ; Radlowski, Emily C. ; Lawrence, Peter ; Zhang, Ying ; Cho, Byung H. ; Segre, Mariangela ; Hess, Rex A. ; Brenna, J. Thomas ; Haschek, Wanda M. ; Nakamura, Manabu T.
Assuntos: Animals ; arachidonic acid ; Brain - drug effects ; Brain - metabolism ; delta-6 desaturase ; Dermatitis - genetics ; Dietary Supplements ; docosahexaenoic acid ; docosapentaenoic acid ; eicosanoid ; essential fatty acid ; FADS3 ; Fatty Acids, Unsaturated - biosynthesis ; Fatty Acids, Unsaturated - metabolism ; Female ; Gene Expression Regulation, Enzymologic ; Gene Knockout Techniques ; Hepatomegaly - genetics ; Infertility, Male - genetics ; Intestines - pathology ; Linoleoyl-CoA Desaturase - deficiency ; Linoleoyl-CoA Desaturase - genetics ; Linoleoyl-CoA Desaturase - metabolism ; Male ; Mice ; Organ Specificity ; Phenotype ; prostaglandin ; Reproduction - genetics ; Skin Ulcer - etiology ; Skin Ulcer - genetics ; Skin Ulcer - metabolism ; Skin Ulcer - pathology ; Splenomegaly - genetics ; Ulcer - etiology ; Ulcer - genetics ; Ulcer - metabolism ; Ulcer - pathology
É parte de: Journal of lipid research, 2009-09, Vol.50 (9), p.1870-1880
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
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Descrição: 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.
Editor: United States: Elsevier Inc
Idioma: Inglês

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

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

United States: Elsevier Inc

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