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 ELOVL4STGD3 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.

Impact of cerebral hypoperfusion–reperfusion on optic nerve integrity and visual function in the DBA/2J mouse model of glaucoma

“…FE was not significantly different between groups at lower spatial frequency (0.033 cycle/degree). In our hands DBA/2J mice did not show a consistent OKHR at baseline which is in accordance with the literature 37. These results were excluded from further analysis.…”

“…In our hands DBA/2J mice did not show a consistent OKHR at baseline which is in accordance with the literature. 37 These results were excluded from further analysis.…”