Elovl4 5-bp-deletion knock-in mice develop progressive photoreceptor degeneration

Invest Ophthalmol Vis Sci. 2006 Oct;47(10):4558-68. doi: 10.1167/iovs.06-0353.


Purpose: To develop and characterize a heterozygous knock-in mouse model carrying the 5-bp deletion in Elovl4 (E_mut+/-) and to study the pathology underlying Stargardt-like macular degeneration (STGD3).

Methods: E_mut+/- mice were generated by targeting a 5-bp deletion (AACTT) in the Elovl4 gene by homologous recombination. E_mut+/- mice of age 2 to 18 months and age-matched wild-type (Wt) littermate control animals were analyzed for the expression of Elovl4 transcript, ELOVL4 protein, photoreceptor-specific genes, and retinal fatty acid composition. Functional retinal changes were evaluated by electroretinography (ERG) and by morphologic and ultrastructural criteria.

Results: E_mut+/- mice retinas showed the presence of both Wt and mutant Elovl4 transcripts and proteins. Morphologic evaluation revealed cone photoreceptor ultrastructural abnormalities as early as 2 months of age, accumulation of lipofuscin in retinal pigment epithelium (RPE), and subretinal deposits at later ages. Shortening of rod outer segments (OS) was observed at approximately 10 months of age. Both cone and rod changes progressed with age. Unlike rod-specific genes, expression of selected cone specific genes was significantly reduced by 7 months of age. Mixed rod-cone and light-adapted b-waves were higher than normal at both 8 and 15 months. Levels of the fatty acids 20:5 (P = 0.027), 22:5 (P = 0.040) and 24:6 (P = 0.005) were found to be significantly lower in the retinas of E_mut+/- mice than in retinas of control subjects.

Conclusions: E_mut+/- animals display characteristic features associated with Stargardt-like macular degeneration and serve as a model for the study of the mechanism underlying STGD3.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Blotting, Western
  • Chromatography, Gas
  • Disease Models, Animal*
  • Disease Progression
  • Electroretinography
  • Eye Proteins / genetics*
  • Fatty Acids / metabolism
  • Gene Expression Regulation / physiology
  • Membrane Proteins / genetics*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mutation*
  • Photoreceptor Cells, Vertebrate / metabolism
  • Photoreceptor Cells, Vertebrate / pathology*
  • Polymerase Chain Reaction
  • Retinal Degeneration / genetics*
  • Retinal Degeneration / metabolism
  • Retinal Degeneration / pathology
  • Sequence Deletion


  • Elovl4 protein, mouse
  • Eye Proteins
  • Fatty Acids
  • Membrane Proteins