Purchase this article with an account.
V. Vasireddy, M.M. Jablonski, M.A. Mandal, D. Prag, X. Wang, L.M. Niziol, D.C. Musch, N. Salem, Jr., P.A. Sieving, R. Ayyagari; Elovl4 5–bp Deletion Knock–In Mice Show Progressive Photoreceptor Degeneration . Invest. Ophthalmol. Vis. Sci. 2006;47(13):4592.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Human autosomal dominant Stargardt–like macular degeneration (STGD3) is associated with a 5–bp deletion(AACTT) mutation in the gene, ELOngation of Very Long chain fatty acid 4 (ELOVL4). This study was designed to generate and characterize a knock–in mouse model with the E lovl4 5–bp deletion (E_mut+/– ).
The E_mut+/– mice were generated on C57BL/6 background by targeting the 5–bp deletion in the Elovl4 gene using homologous recombination. Retinal structure and function of 2 to 12 months old E_mut+/– mice and age matched littermate controls were studied by analyzing morphology, ultrastructure, ERG, expression of Elovl4 and photoreceptor specific genes, ELOVL4 protein and retinal fatty acids.
Presence of both wild type and mutant Elovl4 transcripts was observed in the retinal tissue of E_mut+/– mice. Western blot analysis detected the presence of both forms of the protein. Morphological analysis revealed considerable abnormalities in the photoreceptor layer and accumulation of sub retinal debri. Ultrastructure analysis showed disorganized outer segments, accumulation of partially digested outer segment debri, lipofuscin and melanin granules in the RPE. These morphological changes were found to be progressive over 12 months. Level of expression of selected photoreceptor genes was found to be significantly low in E_mut+/– mice retina by 8 months. Higher a– and b–wave amplitudes were observed in mixed rod–cone as well as cone ERG responses of 8 months old E_mut+/– mice compared to litter mate controls. Levels of 20:5, 22:5 and 24:6 fatty acids were found to be lower (P<0.05) in E_mut+/– retina compared to controls.
The retinal pathology observed in E_mut+/– mice was progressive with age and showed several features resembling the phenotype observed in STGD3 patients with ELOVL4 5–bp deletion mutation. These animals will serve as a valuable model to understand the mechanism underlying STGD3.
This PDF is available to Subscribers Only