title: Elovl4 5-bp-deletion knock-in mice develop progressive photoreceptor degeneration.
abstract: OBJECTIVE
  To develop and characterize a heterozygous knock-in mouse model carrying the 5-bp deletion in Elovl4 (E_mut+/-) and to study the pathology underlying Stargardt-like macular degeneration (STGD3).
  
  
  METHODS
  E_mut+/- mice were generated by targeting a 5-bp deletion (AACTT) in the Elovl4 gene by homologous recombination. E_mut+/- mice of age 2 to 18 months and age-matched wild-type (Wt) littermate control animals were analyzed for the expression of Elovl4 transcript, ELOVL4 protein, photoreceptor-specific genes, and retinal fatty acid composition. Functional retinal changes were evaluated by electroretinography (ERG) and by morphologic and ultrastructural criteria.
  
  
  RESULTS
  E_mut+/- mice retinas showed the presence of both Wt and mutant Elovl4 transcripts and proteins. Morphologic evaluation revealed cone photoreceptor ultrastructural abnormalities as early as 2 months of age, accumulation of lipofuscin in retinal pigment epithelium (RPE), and subretinal deposits at later ages. Shortening of rod outer segments (OS) was observed at approximately 10 months of age. Both cone and rod changes progressed with age. Unlike rod-specific genes, expression of selected cone specific genes was significantly reduced by 7 months of age. Mixed rod-cone and light-adapted b-waves were higher than normal at both 8 and 15 months. Levels of the fatty acids 20:5 (P = 0.027), 22:5 (P = 0.040) and 24:6 (P = 0.005) were found to be significantly lower in the retinas of E_mut+/- mice than in retinas of control subjects.
  
  
  CONCLUSIONS
  E_mut+/- animals display characteristic features associated with Stargardt-like macular degeneration and serve as a model for the study of the mechanism underlying STGD3.
authors.affiliation: Ophthalmology and Visual Sciences, W. K. Kellogg Eye Center, University of Michigan, Ann Arbor, Michigan 48105, USA.
authors.forename: Vidyullatha
authors.initials: V
authors.lastname: Vasireddy
authors.forename: Monica M
authors.initials: MM
authors.lastname: Jablonski
authors.forename: Md Nawajes A
authors.initials: MN
authors.lastname: Mandal
authors.forename: Dorit
authors.initials: D
authors.lastname: Raz-Prag
authors.forename: Xiaofei F
authors.initials: XF
authors.lastname: Wang
authors.forename: Lesli
authors.initials: L
authors.lastname: Nizol
authors.forename: Alessandro
authors.initials: A
authors.lastname: Iannaccone
authors.forename: David C
authors.initials: DC
authors.lastname: Musch
authors.forename: Ronald A
authors.initials: RA
authors.lastname: Bush
authors.forename: Norman
authors.initials: N
authors.lastname: Salem
authors.forename: Paul A
authors.initials: PA
authors.lastname: Sieving
authors.forename: Radha
authors.initials: R
authors.lastname: Ayyagari
mesh_terms: D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D002849:Chromatography, Gas; D004195:Disease Models, Animal; D018450:Disease Progression; D004596:Electroretinography; D005136:Eye Proteins / Q000235:genetics*; D005227:Fatty Acids / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009154:Mutation; D020419:Photoreceptor Cells, Vertebrate / Q000378:metabolism / Q000473:pathology*; D016133:Polymerase Chain Reaction; D012162:Retinal Degeneration / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D017384:Sequence Deletion
chemical_list: C498834:Elovl4 protein, mouse; D005136:Eye Proteins; D005227:Fatty Acids; D008565:Membrane Proteins