title: Elovl4 haploinsufficiency does not induce early onset retinal degeneration in mice.
abstract: ELOVL4 was first identified as a disease-causing gene in Stargardt macular dystrophy (STGD3, MIM 600110.) To date, three ELOVL4 mutations have been identified, all of which result in truncated proteins which induce autosomal dominant juvenile macular degenerations. Based on sequence homology, ELOVL4 is thought to be another member within a family of proteins functioning in the elongation of long chain fatty acids. However, the normal function of ELOVL4 is unclear. We generated Elovl4 knockout mice to determine if Elovl4 loss affects retinal development or function. Here we show that Elovl4 knockout mice, while perinatal lethal, exhibit normal retinal development prior to death at day of birth. Further, postnatal retinal development in Elovl4 heterozygous mice appears normal. Therefore haploinsufficiency for wildtype ELOVL4 in autosomal dominant macular degeneration likely does not contribute to juvenile macular degeneration in STGD3 patients. We found, however, that Elovl4+/- mice exhibit enhanced ERG scotopic and photopic a and b waves relative to wildtype Elovl4+/+ mice suggesting that reduced Elovl4 levels may impact retinal electrophysiological responses.
authors.affiliation: Genetics of Development and Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Wenmei
authors.initials: W
authors.lastname: Li
authors.forename: Yali
authors.initials: Y
authors.lastname: Chen
authors.forename: D Joshua
authors.initials: DJ
authors.lastname: Cameron
authors.forename: Changguan
authors.initials: C
authors.lastname: Wang
authors.forename: Goutam
authors.initials: G
authors.lastname: Karan
authors.forename: Zhenglin
authors.initials: Z
authors.lastname: Yang
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhao
authors.forename: Erik
authors.initials: E
authors.lastname: Pearson
authors.forename: Haoyu
authors.initials: H
authors.lastname: Chen
authors.forename: Chuxia
authors.initials: C
authors.lastname: Deng
authors.forename: Kimberly
authors.initials: K
authors.lastname: Howes
authors.forename: Kang
authors.initials: K
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000818:Animals; D004195:Disease Models, Animal; D004596:Electroretinography; D004910:Erythrocyte Membrane / Q000737:chemistry; D005136:Eye Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D005227:Fatty Acids / Q000097:blood; D006239:Haplotypes; D006801:Humans; D008268:Macular Degeneration / Q000235:genetics* / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012160:Retina / Q000196:embryology / Q000254:growth & development / Q000503:physiopathology; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods
chemical_list: C498834:Elovl4 protein, mouse; D005136:Eye Proteins; D005227:Fatty Acids; D008565:Membrane Proteins