| First Author | Stroud CK | Year | 2009 |
| Journal | J Lipid Res | Volume | 50 |
| Issue | 9 | Pages | 1870-80 |
| PubMed ID | 19351970 | Mgi Jnum | J:153293 |
| Mgi Id | MGI:4361963 | Doi | 10.1194/jlr.M900039-JLR200 |
| Citation | Stroud CK, et al. (2009) Disruption of FADS2 gene in mice impairs male reproduction and causes dermal and intestinal ulceration. J Lipid Res 50:1871-1880 |
| abstractText | Delta-6 desaturase (D6D) catalyzes the first step in the synthesis of highly-unsaturated fatty acids (HUFAs) 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%, whereas a smaller decrease in brain and testis. 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 -/- 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. |
