title: A CTRP5 gene S163R mutation knock-in mouse model for late-onset retinal degeneration.
abstract: Late-onset retinal macular degeneration (L-ORD) is an autosomal dominant inherited disorder caused by a single missense mutation (S163R) in the CTRP5/C1QTNF5 protein. Early phenotypic features of L-ORD include: dark adaptation abnormalities, nyctalopia, and drusen deposits in the peripheral macular region. Apart from posterior segment abnormalities, these patients also develop abnormally long anterior lens zonules. In the sixth decade of life the rod and cone function declines, accompanied by electroretinogram (ERG) abnormalities. Some patients also develop choroidal neovascularization and glaucoma. In order to understand the disease pathology and mechanisms involved in retinal dystrophy, we generated a knock-in (Ctrp5(+/-)) mouse model carrying the disease-associated mutation in the mouse Ctrp5/C1QTNF5 gene. These mice develop slower rod-b wave recovery consistent with early dark adaptation abnormalities, accumulation of hyperautofluorescence spots, retinal pigment epithelium abnormalities, drusen, Bruch's membrane abnormalities, loss of photoreceptors, and retinal vascular leakage. The Ctrp5(+/-) mice, which have most of the pathological features of age-related macular degeneration, are unique and may serve as a valuable model both to understand the molecular pathology of late-onset retinal degeneration and to evaluate therapies.
authors.affiliation: Ophthalmology, University of California San Diego, La Jolla, CA 92037, USA.
authors.forename: Venkata R M
authors.initials: VR
authors.lastname: Chavali
authors.forename: Naheed W
authors.initials: NW
authors.lastname: Khan
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Cukras
authors.forename: Dirk-Uwe
authors.initials: DU
authors.lastname: Bartsch
authors.forename: Monica M
authors.initials: MM
authors.lastname: Jablonski
authors.forename: Radha
authors.initials: R
authors.lastname: Ayyagari
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000235:genetics; D055879:Gene Knock-In Techniques; D023061:Gene Order; D018390:Gene Targeting; D006579:Heterozygote; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D020125:Mutation, Missense / Q000235:genetics*; D010641:Phenotype; D010786:Photoreceptor Cells / Q000378:metabolism; D012160:Retina / Q000473:pathology; D012162:Retinal Degeneration / Q000235:genetics* / Q000473:pathology; D013312:Stress, Physiological / Q000235:genetics
chemical_list: C516596:CTRP5 protein, mouse; D008565:Membrane Proteins