title: Ccl2/Cx3cr1-deficient mice: an animal model for age-related macular degeneration.
abstract: OBJECTIVE
  Senescent Ccl2-/- mice develop cardinal features of human age-related macular degeneration (AMD). Loss-of-function single-nucleotide polymorphisms within CX3CR1 are associated with AMD.
  
  
  METHODS
  We generated Ccl2-/-/Cx3cr1-/- [double-knockout (DKO)] mice and evaluated the eyes using fundoscopy routine histology, immunochemistry, biochemistry and proteomics.
  
  
  RESULTS
  At 6 weeks old, all DKO mice developed AMD-like retinal lesions such as abnormal retinal pigment epithelium cells, drusen, photoreceptor atrophy and choroidal neovascularization, which progressed with age and reversed with high omega-3 long-chain polyunsaturated fatty acid diet. N-retinylidene-N-retinylethanolamine (A2E), a major lipofuscin fluorophore, illustrated by an emission peak at approximately 600 nm, was significantly higher in DKO retinal pigment epithelium. Decreased ERp29 was found in the retina of DKO mice.
  
  
  CONCLUSIONS
  A broad spectrum of AMD pathologies with early onset and high penetrance in these mice implicate certain chemokines, A2E and endoplasmic reticulum proteins in AMD pathogenesis.
authors.affiliation: Section of Immunopathology, Laboratory of Immunology, National Eye Institute, Bethesda, MD 20892-1857, USA. chanc@nei.nih.gov
authors.forename: Chi-Chao
authors.initials: CC
authors.lastname: Chan
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Ross
authors.forename: Defen
authors.initials: D
authors.lastname: Shen
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Ding
authors.forename: Zigurts
authors.initials: Z
authors.lastname: Majumdar
authors.forename: Christine M
authors.initials: CM
authors.lastname: Bojanowski
authors.forename: Min
authors.initials: M
authors.lastname: Zhou
authors.forename: Norman
authors.initials: N
authors.lastname: Salem
authors.forename: Robert
authors.initials: R
authors.lastname: Bonner
authors.forename: Jingsheng
authors.initials: J
authors.lastname: Tuo
mesh_terms: D000818:Animals; D000073883:CX3C Chemokine Receptor 1; D018932:Chemokine CCL2 / Q000172:deficiency*; D016207:Cytokines; D004195:Disease Models, Animal; D018450:Disease Progression; D008268:Macular Degeneration / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D010857:Pigment Epithelium of Eye / Q000378:metabolism* / Q000648:ultrastructure; D019707:Receptors, Chemokine / Q000172:deficiency*
chemical_list: D000073883:CX3C Chemokine Receptor 1; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; C471885:Cx3cr1 protein, mouse; D016207:Cytokines; D019707:Receptors, Chemokine