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

Abstract:

: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.

journal_name

J Lipid Res

authors

Stroud CK,Nara TY,Roqueta-Rivera M,Radlowski EC,Lawrence P,Zhang Y,Cho BH,Segre M,Hess RA,Brenna JT,Haschek WM,Nakamura MT

doi

10.1194/jlr.M900039-JLR200

subject

Has Abstract

pub_date

2009-09-01 00:00:00

pages

1870-80

issue

9

eissn

0022-2275

issn

1539-7262

pii

M900039-JLR200

journal_volume

50

pub_type

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