title: Mouse Models of Stargardt 3 Dominant Macular Degeneration.
abstract: Stargardt type 3 macular degeneration is dependent on a dominant defect in a single gene, ELOVL4 (elongase of very long chain fatty acids 4). The encoded enzyme, ELOVL4, is required for the synthesis of very long chain polyunsaturated fatty acids (VLC-PUFAs), a rare class of > C24 lipids. In vitro expression studies suggest that mutated ELOVL4(STGD3) proteins fold improperly, resulting in ER stress and formation of cytosolic aggresomes of wild type and mutant ELOVL4. Although a number of mouse models have been developed to determine whether photoreceptor cell loss in STGD3 results from depletion of VLC-PUFAs, aggresome-dependent cell stress or a combination of these two factors, none of these models adequately recapitulates the disease phenotype in humans. Thus, the precise molecular mechanism by which ELOVL4 mutation causes photoreceptor degeneration in mice and in human patients remains to be characterized. This mini review compares and evaluates current STGD3 mouse models and determines what conclusions can be drawn from past work.
authors.affiliation: Department of Ophthalmology and Visual Sciences, John A. Moran Eye Institute, University of Utah School of Medicine, 84132, Salt Lake City, UT, USA. peter.barabas@utah.edu.
authors.forename: Peter
authors.initials: P
authors.lastname: Barabas
authors.affiliation: Department of Ophthalmology and Visual Sciences, John A. Moran Eye Institute, University of Utah School of Medicine, 84132, Salt Lake City, UT, USA. aruna.gorusupudi@utah.edu.
authors.forename: Aruna
authors.initials: A
authors.lastname: Gorusupudi
authors.affiliation: Department of Ophthalmology and Visual Sciences, John A. Moran Eye Institute, University of Utah School of Medicine, 84132, Salt Lake City, UT, USA. paul.bernstein@hsc.utah.edu.
authors.forename: Paul S
authors.initials: PS
authors.lastname: Bernstein
authors.affiliation: Department of Ophthalmology and Visual Sciences, John A. Moran Eye Institute, University of Utah School of Medicine, 84132, Salt Lake City, UT, USA. david.krizaj@hsc.utah.edu.
authors.forename: David
authors.initials: D
authors.lastname: Krizaj
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005136:Eye Proteins / Q000235:genetics*; D005231:Fatty Acids, Unsaturated / Q000096:biosynthesis; D006801:Humans; D008268:Macular Degeneration / Q000151:congenital* / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics*; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009154:Mutation; D000080362:Stargardt Disease
chemical_list: C498834:Elovl4 protein, mouse; D005136:Eye Proteins; D005231:Fatty Acids, Unsaturated; D008565:Membrane Proteins
keywords: Cre; ELOVL4; Knock-in mice; Knock-out mice; Phenotype; STGD3; Transgenic mice; Very long chain polyunsaturated fatty acids (VLC-PUFAs); pLox