Mouse Models of Stargardt 3 Dominant Macular Degeneration

  • Peter Barabas
  • Aruna Gorusupudi
  • Paul S Bernstein
  • David Krizaj
Conference paper
First Online:
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 854)

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.

Keywords

ELOVL4 STGD3 Very long chain polyunsaturated fatty acids (VLC-PUFAs) Transgenic mice Knock-in mice Knock-out mice pLox Cre Phenotype 
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Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  • Peter Barabas
    • 1
  • Aruna Gorusupudi
    • 1
  • Paul S Bernstein
    • 1
  • David Krizaj
    • 1
  1. 1.Department of Ophthalmology and Visual Sciences, John A. Moran Eye InstituteUniversity of Utah School of MedicineSalt Lake CityUSA

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