title: A Stargardt disease-3 mutation in the mouse Elovl4 gene causes retinal deficiency of C32-C36 acyl phosphatidylcholines.
abstract: 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.
authors.affiliation: Department of Ophthalmology, The University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA.
authors.forename: Anne
authors.initials: A
authors.lastname: McMahon
authors.forename: Shelley N
authors.initials: SN
authors.lastname: Jackson
authors.forename: Amina S
authors.initials: AS
authors.lastname: Woods
authors.forename: Wojciech
authors.initials: W
authors.lastname: Kedzierski
mesh_terms: 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
chemical_list: D002457:Cell Extracts; C498834:Elovl4 protein, mouse; D005136:Eye Proteins; D008565:Membrane Proteins; D010713:Phosphatidylcholines; D012333:RNA, Messenger