title: Genetically engineered large animal model for studying cone photoreceptor survival and degeneration in retinitis pigmentosa.
abstract: Patients with retinitis pigmentosa (RP) typically develop night blindness early in life due to loss of rod photoreceptors. The remaining cone photoreceptors are the mainstay of their vision; however, over years or decades, these cones slowly degenerate, leading to blindness. We created transgenic pigs that express a mutated rhodopsin gene (Pro347Leu). Like RP patients with the same mutation, these pigs have early and severe rod loss; initially their cones are relatively spared, but these surviving cones slowly degenerate. By age 20 months, there is only a single layer of morphologically abnormal cones and the cone electroretinogram is markedly reduced. Given the strong similarities in phenotype to that of RP patients, these transgenic pigs will provide a large animal model for study of the protracted phase of cone degeneration found in RP and for preclinical treatment trials.
authors.affiliation: Department of Animal Science, North Carolina State University, Raleigh, USA.
authors.forename: R M
authors.initials: RM
authors.lastname: Petters
authors.forename: C A
authors.initials: CA
authors.lastname: Alexander
authors.forename: K D
authors.initials: KD
authors.lastname: Wells
authors.forename: E B
authors.initials: EB
authors.lastname: Collins
authors.forename: J R
authors.initials: JR
authors.lastname: Sommer
authors.forename: M R
authors.initials: MR
authors.lastname: Blanton
authors.forename: G
authors.initials: G
authors.lastname: Rojas
authors.forename: Y
authors.initials: Y
authors.lastname: Hao
authors.forename: W L
authors.initials: WL
authors.lastname: Flowers
authors.forename: E
authors.initials: E
authors.lastname: Banin
authors.forename: A V
authors.initials: AV
authors.lastname: Cideciyan
authors.forename: S G
authors.initials: SG
authors.lastname: Jacobson
authors.forename: F
authors.initials: F
authors.lastname: Wong
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D015139:Blotting, Southern; D004195:Disease Models, Animal; D004596:Electroretinography; D004624:Embryo Transfer; D005786:Gene Expression Regulation / Q000235:genetics; D005818:Genetic Engineering; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012160:Retina / Q000473:pathology / Q000503:physiopathology* / Q000648:ultrastructure; D017949:Retinal Cone Photoreceptor Cells / Q000503:physiopathology* / Q000648:ultrastructure; D012162:Retinal Degeneration / Q000503:physiopathology; D012174:Retinitis Pigmentosa / Q000235:genetics* / Q000503:physiopathology; D012243:Rhodopsin / Q000737:chemistry / Q000235:genetics; D013552:Swine / Q000196:embryology / Q000235:genetics*; D019076:Transgenes
chemical_list: D012243:Rhodopsin