title: Production of ELOVL4 transgenic pigs: a large animal model for Stargardt-like macular degeneration.
abstract: BACKGROUND
  Truncation mutations in the elongation of very long chain fatty acids-4 (AF277094, MIM #605512) (ELOVL4) gene cause Stargardt-like macular dystrophy type 3 (STGD3). Mice expressing truncated ELOVL4 develop rapid retinal degeneration, but are poor STGD3 models since mice lack a macula. Photoreceptor topography in the pig retina is more similar to that in humans as it includes the cone rich, macula-like area centralis. The authors generated transgenic pigs expressing human disease-causing ELOVL4 mutations to better model the pathobiology of this macular disease.
  
  
  METHODS
  Pronuclear DNA microinjection and somatic cell nuclear transfer were used to produce transgenic pigs for two different ELOVL4 mutations: the 5 base pair deletion (5 bpdel) and the 270 stop mutation (Y270terEYFP). Retinal transgene expression, morphology and electrophysiology were examined.
  
  
  RESULTS
  The authors obtained four lines of Y270terEYFP and one line of 5 bpdel transgenic animals. Direct fluorescence microscopy indicated that the Y270terEYFP protein is expressed in photoreceptors and mislocalised within the cell. Immunohistochemical examination of transgenic pigs showed photoreceptor loss and disorganised inner and outer segments. Electroretinography demonstrated diminished responses in both transgenic models.
  
  
  CONCLUSIONS
  These transgenic pigs provide unique animal models for examining macular degeneration and STGD3 pathogenesis.
authors.affiliation: Department of Animal Science, North Carolina State University, Raleigh, North Carolina, USA.
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Sommer
authors.forename: Jose L
authors.initials: JL
authors.lastname: Estrada
authors.forename: Edwin B
authors.initials: EB
authors.lastname: Collins
authors.forename: Matthew
authors.initials: M
authors.lastname: Bedell
authors.forename: Curtis A
authors.initials: CA
authors.lastname: Alexander
authors.forename: Zhenglin
authors.initials: Z
authors.lastname: Yang
authors.forename: Guy
authors.initials: G
authors.lastname: Hughes
authors.forename: Bashir
authors.initials: B
authors.lastname: Mir
authors.forename: Brian C
authors.initials: BC
authors.lastname: Gilger
authors.forename: Seanna
authors.initials: S
authors.lastname: Grob
authors.forename: Xinran
authors.initials: X
authors.lastname: Wei
authors.forename: Jorge A
authors.initials: JA
authors.lastname: Piedrahita
authors.forename: Peter X
authors.initials: PX
authors.lastname: Shaw
authors.forename: Robert M
authors.initials: RM
authors.lastname: Petters
authors.forename: Kang
authors.initials: K
authors.lastname: Zhang
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D004195:Disease Models, Animal; D004596:Electroretinography; D005136:Eye Proteins / Q000096:biosynthesis* / Q000235:genetics; D017353:Gene Deletion; D007150:Immunohistochemistry; D008268:Macular Degeneration / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics; D008856:Microscopy, Fluorescence; D009154:Mutation; D012160:Retina / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D013552:Swine
chemical_list: D005136:Eye Proteins; D008565:Membrane Proteins