title: The role of complement dysregulation in AMD mouse models.
abstract: Variations in several complement genes are now known to be significant risk factors for the development of age-related macular degeneration (AMD). Despite dramatic effects on disease susceptibility, the underlying mechanisms by which common polymorphisms in complement proteins alter disease risk have remained unclear. Genetically modified mice in which the activity of the complement has been altered are available and can be used to investigate the role of complement in the pathogenesis of AMD. In this mini review, we will discuss some existing complement models of AMD and our efforts to develop and characterize the ocular phenotype in a variety of mice in which complement is either chronically activated or inhibited. A spectrum of complement dysregulation was modeled on the APOE4 AMD mouse model by crossing these mice to complement factor H knockout (cfh-/-) mice to test the impact of excess complement activation, and by crossing them to soluble-complement-receptor-1-related protein y (sCrry) mice, in which sCrry acts as a potent inhibitor of mouse complement acting in a manner similar to CFH. In addition, we have also generated humanized CFH mice expressing normal and risk variants of CFH.
authors.affiliation: Department of Ophthalmology, Duke University Medical Center, 2351 Erwin Rd, 27710, Durham, NC, USA, jd84@duke.edu.
authors.forename: Jin-Dong
authors.initials: JD
authors.lastname: Ding
authors.forename: Una
authors.initials: U
authors.lastname: Kelly
authors.forename: Marybeth
authors.initials: M
authors.lastname: Groelle
authors.forename: Joseph G
authors.initials: JG
authors.lastname: Christenbury
authors.forename: Wenlan
authors.initials: W
authors.lastname: Zhang
authors.forename: Catherine
authors.initials: C
authors.lastname: Bowes Rickman
mesh_terms: D000818:Animals; D017242:Complement Factor H / Q000172:deficiency* / Q000235:genetics / Q000276:immunology*; D003165:Complement System Proteins / Q000276:immunology*; D004195:Disease Models, Animal; D000081208:Hereditary Complement Deficiency Diseases; D006801:Humans; D007674:Kidney Diseases / Q000276:immunology*; D008268:Macular Degeneration / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D015432:Glomerulonephritis, Membranoproliferative
chemical_list: D017242:Complement Factor H; D003165:Complement System Proteins