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
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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