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A Stargardt disease‐3 mutation in the mouse Elovl4 gene causes retinal deficiency of C32–C36 acyl phosphatidylcholines
Author(s) -
McMahon Anne,
Jackson Shelley N.,
Woods Amina S.,
Kedzierski Wojciech
Publication year - 2007
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2007.10.050
Subject(s) - endoplasmic reticulum , mutant , mutation , biology , fatty acid desaturase , unfolded protein response , retinal degeneration , retinal , biochemistry , fatty acid , gene , polyunsaturated fatty acid
Stargardt disease‐3 (STGD3) is a juvenile dominant macular degeneration caused by mutations in elongase of very long chain fatty acid‐4. All identified mutations produce a truncated protein which lacks a motif for protein retention in endoplasmic reticulum, the site of fatty acid synthesis. In these studies of Stgd3‐knockin mice carrying a human pathogenic mutation, we examined two potential pathogenic mechanisms: truncated protein‐induced cellular stress and lipid product deficiency. Analysis of mutant retinas detected no cellular stress but demonstrated selective deficiency of C32–C36 acyl phosphatidylcholines. We conclude that this deficit leads to the human STGD3 pathology.