Ciliary genes arl13b, ahi1 and cc2d2a differentially modify expression of visual acuity phenotypes but do not enhance retinal degeneration due to mutation of cep290 in zebrafish
Autor: | Brian D Perkins, Ping Song, Ellen Piccillo, Emma M. Lessieur, Richard Rozic, Joseph Fogerty, Gabrielle C Nivar |
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Přispěvatelé: | Neuhauss, Stephan CF |
Jazyk: | angličtina |
Rok vydání: | 2019 |
Předmět: |
Retinal degeneration
genetic structures Mutant Vesicular Transport Proteins Visual Acuity Neurodegenerative Eye medicine.disease_cause Animals Genetically Modified 2.1 Biological and endogenous factors Aetiology Zebrafish Pediatric 0303 health sciences Mutation Multidisciplinary biology ADP-Ribosylation Factors Cilium Retinal Degeneration 030305 genetics & heredity Cell biology Rhodopsin Retinal Cone Photoreceptor Cells Medicine Transducin Microtubule-Associated Proteins Biotechnology General Science & Technology Cell Survival Science Nonsense mutation Genetically Modified CC2D2A Joubert syndrome 03 medical and health sciences Rare Diseases Retinitis pigmentosa Genetics medicine Animals Humans Cilia Eye Disease and Disorders of Vision 030304 developmental biology Animal Neurosciences Zebrafish Proteins medicine.disease biology.organism_classification eye diseases Disease Models Animal Disease Models biology.protein Congenital Structural Anomalies sense organs Carrier Proteins |
Zdroj: | PLoS ONE, Vol 14, Iss 4, p e0213960 (2019) PloS one, vol 14, iss 4 |
ISSN: | 1932-6203 |
Popis: | Mutations in the gene Centrosomal Protein 290 kDa (CEP290) result in multiple ciliopathies ranging from the neonatal lethal disorder Meckel-Gruber Syndrome to multi-systemic disorders such as Joubert Syndrome and Bardet-Biedl Syndrome to nonsyndromic diseases like Leber Congenital Amaurosis (LCA) and retinitis pigmentosa. Results from model organisms and human genetics studies, have suggest that mutations in genes encoding protein components of the transition zone (TZ) and other cilia-associated proteins can function as genetic modifiers and be a source forCEP290pleiotropy. We investigated the zebrafishcep290fh297/fh297mutant, which encodes a nonsense mutation (p.Q1217*). This mutant is viable as adults, exhibits scoliosis, and undergoes a slow, progressive cone degeneration. Thecep290fh297/fh297mutants showed partial mislocalization of the transmembrane protein rhodopsin but not of the prenylated proteins rhodopsin kinase (GRK1) or the rod transducin subunit GNB1. Surprisingly, photoreceptor degeneration did not trigger proliferation of Müller glia, but proliferation of rod progenitors in the outer nuclear layer was significantly increased. To determine if heterozygous mutations in other cilia genes could exacerbate retinal degeneration, we bredcep290fh297/fh297mutants toarl13b, ahi1,andcc2d2amutant zebrafish lines. Whilecep290fh297/fh297mutants lacking a single allele of these genes did not exhibit accelerated photoreceptor degeneration, loss of one alleles ofarl13borahi1reduced visual performance in optokinetic response assays at 5 days post fertilization. Our results indicate that thecep290fh297/fh297mutant is a useful model to study the role of genetic modifiers on photoreceptor degeneration in zebrafish and to explore how progressive photoreceptor degeneration influences regeneration in adult zebrafish.Nonstandard abbreviationsBBSBardet-Biedl SyndromeCOScone outer segmentsDpfDays post fertilizationGNB1rod transducin β subunitGRK1rhodopsin kinaseJTBSJoubert SyndromeLCALeber Congenital AmaurosisMKSMeckel SyndromeNPHPnephronophthisisOKRoptokinetic responsePNApeanut agglutinin lectinROSrod outer segmentsRP2Retinitis Pigmentosa 2 |
Databáze: | OpenAIRE |
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