Elovl4 haploinsufficiency does not induce early onset retinal degeneration in mice.
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.
Li
Wenmei
W
Genetics of Development and Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
Chen
Yali
Y
Cameron
D Joshua
DJ
Wang
Changguan
C
Karan
Goutam
G
Yang
Zhenglin
Z
Zhao
Yu
Y
Pearson
Erik
E
Chen
Haoyu
H
Deng
Chuxia
C
Howes
Kimberly
K
Zhang
Kang
K
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
C498834:Elovl4 protein, mouse; D005136:Eye Proteins; D005227:Fatty Acids; D008565:Membrane Proteins