A Stargardt disease-3 mutation in the mouse Elovl4 gene causes retinal deficiency of C32-C36 acyl phosphatidylcholines.
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.
McMahon
Anne
A
Department of Ophthalmology, The University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA.
Jackson
Shelley N
SN
Woods
Amina S
AS
Kedzierski
Wojciech
W
D000818:Animals; D002457:Cell Extracts; D005136:Eye Proteins / Q000235:genetics* / Q000378:metabolism*; D006579:Heterozygote; D013058:Mass Spectrometry; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D010713:Phosphatidylcholines / Q000737:chemistry / Q000172:deficiency* / Q000378:metabolism*; D017510:Protein Folding; D012333:RNA, Messenger / Q000235:genetics; D012160:Retina / Q000378:metabolism
D002457:Cell Extracts; C498834:Elovl4 protein, mouse; D005136:Eye Proteins; D008565:Membrane Proteins; D010713:Phosphatidylcholines; D012333:RNA, Messenger