title: Viral-mediated vision rescue of a novel AIPL1 cone-rod dystrophy model.
abstract: Defects in aryl hydrocarbon receptor interacting protein-like1 (AIPL1) are associated with blinding diseases with a wide range of severity in humans. We examined the mechanism behind autosomal dominant cone-rod dystrophy (adCORD) caused by 12 base pair (bp) deletion at proline 351 of hAIPL1 (P351Δ12) mutation in the primate-specific region of human AIPL1. Mutant P351Δ12 human isoform, aryl hydrocarbon receptor interacting protein-like 1 (hAIPL1) mice demonstrated a CORD phenotype with early defects in cone-mediated vision and subsequent photoreceptor degeneration. A dominant CORD phenotype was observed in double transgenic animals expressing both mutant P351Δ12 and normal hAIPL1, but not with co-expression of P351Δ12 hAIPL1 and the mouse isoform, aryl hydrocarbon receptor interacting protein-like 1 (mAipl1). Despite a dominant effect of the mutation, we successfully rescued cone-mediated vision in P351Δ12 hAIPL1 mice following high over-expression of WT hAIPL1 by adeno-associated virus-mediated gene delivery, which was stable up to 6 months after treatment. Our transgenic P351Δ12 hAIPL1 mouse offers a novel model of AIPL1-CORD, with distinct defects from both the Aipl1-null mouse mimicking LCA and the Aipl1-hypomorphic mice mimicking a slow progressing RP.
authors.affiliation: Center for Neuroscience Department of Ophthalmology and cku@mix.wvu.edu ramamurthyv@wvuhealthcare.com.
authors.forename: Cristy A
authors.initials: CA
authors.lastname: Ku
authors.affiliation: Department of Ophthalmology, University of Florida, Gainesville, FL 32610, USA and.
authors.forename: Vince A
authors.initials: VA
authors.lastname: Chiodo
authors.affiliation: Department of Ophthalmology, University of Florida, Gainesville, FL 32610, USA and.
authors.forename: Sanford L
authors.initials: SL
authors.lastname: Boye
authors.affiliation: Department of Ophthalmology and Department of Biochemistry, Robert C. Byrd Health Sciences Center, West Virginia University, Morgantown, WV 26505, USA.
authors.forename: Abigail
authors.initials: A
authors.lastname: Hayes
authors.affiliation: Eye Research Institute, Oakland University, Rochester, MI 48309, USA.
authors.forename: Andrew F X
authors.initials: AF
authors.lastname: Goldberg
authors.affiliation: Department of Ophthalmology, University of Florida, Gainesville, FL 32610, USA and.
authors.forename: William W
authors.initials: WW
authors.lastname: Hauswirth
authors.affiliation: Center for Neuroscience Department of Ophthalmology and Department of Biochemistry, Robert C. Byrd Health Sciences Center, West Virginia University, Morgantown, WV 26505, USA cku@mix.wvu.edu ramamurthyv@wvuhealthcare.com.
authors.forename: Visvanathan
authors.initials: V
authors.lastname: Ramamurthy
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism*; D000229:Dependovirus / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005136:Eye Proteins / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000008:administration & dosage; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D017949:Retinal Cone Photoreceptor Cells / Q000473:pathology; D012174:Retinitis Pigmentosa / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D017384:Sequence Deletion
chemical_list: C403625:AIPL1 protein, human; D048868:Adaptor Proteins, Signal Transducing; C498604:Aipl1 protein, mouse; D002352:Carrier Proteins; D005136:Eye Proteins