Role of Stargardt-3 macular dystrophy protein (ELOVL4) in the biosynthesis of very long chain fatty acids

• DOI: 10.1073/pnas.0802607105
• Publication Date: 2008-08-27T00:45:01Z
• Authors: Martin-Paul Agbaga; Richard S. Brush; Md Nawajes A. Mandal; Kimberly Henry; Michael H. Elliott; Robert E. Anderson
• Keywords: Macular dystrophy; Stargardt disease; Dystrophy

Stargardt-like macular dystrophy (STGD3) is a dominantly inherited juvenile degeneration that eventually leads to loss of vision. Three independent mutations causing STGD3 have been identified in exon six gene named Elongation very long chain fatty acids 4 (ELOVL4). The ELOVL4 protein was predicted be involved acid elongation, although evidence for this and the specific step(s) it may catalyze remained elusive. Here, using gain-of-function approach, we provide direct compelling required synthesis C28 C30 saturated (VLC-FA) C28-C38 polyunsaturated (VLC-PUFA), latter being uniquely expressed retina, sperm, brain. Rat neonatal cardiomyocytes human retinal epithelium cell line (ARPE-19) were transduced with recombinant adenovirus type 5 carrying mouse Elovl4 supplemented 24:0, 20:5n3, or 22:5n3. 24:0 elongated 28:0 30:0; 20:5n3 22:5n3 series PUFA. Because only known phenotype disease, propose reduced VLC-PUFA retinas these patients cause photoreceptor death.