The role of dietary arachidonic acid and docosahexaenoic acid in preventing the phenotype observed with highly unsaturated fatty acid deficiency
type: CreativeWork
description: The physiological roles of highly unsaturated fatty acids (HUFA), mainly arachidonic acid (AA, 20:4ω6) and docosahexaenoic acid (DHA, 22:6ω3), are not completely understood. In order to study specific functions for AA and DHA, a delta-6 desaturase knockout (D6D-/-) mouse was created. D6D is a key enzyme in synthesizing HUFA from the precursor dietary essential fatty acids, linoleic acid (LA, 18:2ω6) or α-linolenic acid (ALA, 18:3ω3). By disrupting D6D expression, LA and ALA provided in the diet will not be metabolized to HUFA. Phenotype of the D6D-/- mouse is therefore specific to lack of AA and/or DHA and consists of ulcerative dermatitis, male infertility, gastrointestinal ulcers, and hepatic lipidosis. New insight on specific AA and DHA roles was established through dietary prevention of HUFA deficiency phenotype. The absence of a D6D isozyme had to be assessed before further characterizing HUFA roles with the D6D-/- mouse model. The presence of a D6D isozyme would interfere with the creation of HUFA deficiency. The primary D6D isozyme candidate was Fads3 gene due to its increased gene expression in D6D-/- liver and homology to the Fads2 gene that encodes for D6D. Cloning and transfection of Fads3 into cultured HEK293 cells confirmed lack of D6D activity (Chapter 3). The order of appearance of D6D-/- phenotype due to HUFA deficiency had yet to be determined. A D6D-/- time course study (Chapter 4) characterized the mouse at different ages in order to follow sequence of HUFA deficiency pathology. The amount of HUFA in D6D-/- at weaning was comparable to control mouse indicating the presence of HUFA stores that most likely result from HUFA passed on from the mother. Subsequent HUFA depletion with age correlated with severity of D6D-/- phenotype. Male infertility, gastrointestinal erosions, and hepatic lipidosis are the first observed HUFA deficiency phenotype to appear at 6 weeks of age, followed by impaired antibody response at 9 weeks, and ulcerative dermatitis by…
abstract: The physiological roles of highly unsaturated fatty acids (HUFA), mainly arachidonic acid (AA, 20:4ω6) and docosahexaenoic acid (DHA, 22:6ω3), are not completely understood. In order to study specific functions for AA and DHA, a delta-6 desaturase knockout (D6D-/-) mouse was created. D6D is a key enzyme in synthesizing HUFA from the precursor dietary essential fatty acids, linoleic acid (LA, 18:2ω6) or α-linolenic acid (ALA, 18:3ω3). By disrupting D6D expression, LA and ALA provided in the diet will not be metabolized to HUFA. Phenotype of the D6D-/- mouse is therefore specific to lack of AA and/or DHA and consists of ulcerative dermatitis, male infertility, gastrointestinal ulcers, and hepatic lipidosis. New insight on specific AA and DHA roles was established through dietary prevention of HUFA deficiency phenotype. The absence of a D6D isozyme had to be assessed before further characterizing HUFA roles with the D6D-/- mouse model. The presence of a D6D isozyme would interfere with the creation of HUFA deficiency. The primary D6D isozyme candidate was Fads3 gene due to its increased gene expression in D6D-/- liver and homology to the Fads2 gene that encodes for D6D. Cloning and transfection of Fads3 into cultured HEK293 cells confirmed lack of D6D activity (Chapter 3). The order of appearance of D6D-/- phenotype due to HUFA deficiency had yet to be determined. A D6D-/- time course study (Chapter 4) characterized the mouse at different ages in order to follow sequence of HUFA deficiency pathology. The amount of HUFA in D6D-/- at weaning was comparable to control mouse indicating the presence of HUFA stores that most likely result from HUFA passed on from the mother. Subsequent HUFA depletion with age correlated with severity of D6D-/- phenotype. Male infertility, gastrointestinal erosions, and hepatic lipidosis are the first observed HUFA deficiency phenotype to appear at 6 weeks of age, followed by impaired antibody response at 9 weeks, and ulcerative dermatitis by…
author: Roqueta Rivera, Manuel
language: en
keywords: Essential fatty acids, highly unsaturated fatty acids, arachidonic acid, Docosahexaenoic acid (DHA)
date published: 2010-05-14T20:43:46Z
date modified: 2026-07-22T22:25:08Z
provider: University of Illinois - Urbana-Champaign
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Illinois at Urbana-Champaign

PropertyValue
property ID: Handle
value: http://hdl.handle.net/2142/15515