Zebrafish as a Developmental Model Organism for Pediatric Research

Veldman, Matthew B.; Lin, Shuo

doi:10.1203/pdr.0b013e318186e609

Cited by 168 publications

(111 citation statements)

References 70 publications

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“…Zebrafish have surged in importance as an animal model in almost every field of medicine, [9][10][11] owing to their publicly available genomic sequence, 12 their external fertilization, rapid development, accessibility of embryos (larvae) and the evolutionary conservation of the vertebrate body plan. Their precocious development of vision and remarkable evolutionary conservation of the eye make the zebrafish retina an excellent model for human visual disorders.…”

Section: Introductionmentioning

confidence: 99%

Gucy2f zebrafish knockdown – a model for Gucy2d-related leber congenital amaurosis

et al. 2012

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Mutations in retinal-specific guanylate cyclase (Gucy2d) are associated with Leber congenital amaurosis-1 (LCA1). Zebrafish offer unique advantages relative to rodents, including their excellent color vision, precocious retinal development, robust visual testing strategies, low cost, relatively easy transgenesis and shortened experimental times. In this study we will demonstrate the feasibility of using gene-targeting in the zebrafish as a model for the photoreceptor-specific GUCY2D-related LCA1, by reporting the visual phenotype and retinal histology resulting from Gucy2f knockdown. Gucy2f zebrafish LCA-orthologous cDNA was identified and isolated by PCR amplification. Its expression pattern was determined by whole-mount in-situ hybridization and its function was studied by gene knockdown using two different morpholino-modified oligos (MO), one that blocks translation of Gucy2f and one that blocks splicing of Gucy2f. Visual function was assessed with an optomotor assay on 6-days-postfertilization larvae, and by analyzing changes in retinal histology. Gucy2f knockdown resulted in significantly lower vision as measured by the optomotor response compared with uninjected and control MO-injected zebrafish larvae. Histological changes in the Gucy2f-knockdown larvae included loss and shortening of cone and rod outer segments. A zebrafish model of Gucy2f-related LCA1 displays early visual dysfunction and photoreceptor layer dystrophy. This study serves as proof of concept for the use of zebrafish as a simple, inexpensive model with excellent vision on which further study of LCA-related genes is possible. Keywords: leber congenital amaurosis; animal model; GUCY2D; optomotor assay INTRODUCTION Leber congenital amaurosis (LCA) is a family of severe, early-onset, autosomal-recessive forms of pediatric blindness. LCA has been linked to more than 16 genes, often exhibiting clinical heterogeneity. 1,2 LCA1 is caused by mutations in the gene GUCY2D, which encodes the retinal Gucy2d-1 (GC1) and accounts for B20% of all cases of LCA. 3 LCA2 is caused by mutations in the RPE65 gene, which is expressed in the retinal pigment epithelium. Breakthrough research has demonstrated visual improvement following gene therapy trials in humans with LCA2. 4,5 Human trials relied on a decade of proof-of-concept studies in canine and rodent models. 6-8 Unlike LCA2, in which gene therapy is aimed at correcting an RPE defect, searching for gene therapy for LCA1 will involve an attempt at treating the photoreceptors. European Journal of Human GeneticsResearch in inherited retinal disease relies heavily on animal models, commonly mammals such as mice and dogs. These animal models have significant advantages, including the availability of knockout technology. Two specific drawbacks slow the applicability of rodent or canine models for study of relatively rare genetic diseases such as LCA and other retinal dystrophies. The first difficulty is the high cost and length of time required to create a new knockout line; thus, it is applicable only for comm...

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Section: Introductionmentioning

confidence: 99%

Gucy2f zebrafish knockdown – a model for Gucy2d-related leber congenital amaurosis

et al. 2012

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“…Recently, Howe et al (2017) reported based on OMIM (Online Mendelian Inheritance in Man) tool that 82% of the genes involved in human disorders bear a strong resemblance with zebrafish. Zebrafish research is also guiding us to understanding the fundamental aspects of developmental stages (Van Slyke et al, 2014), embryogenesis (Veldman and Lin, 2008), fertility (Hoo et al, 2016) and treating human disease (Santoriello and Zon, 2012). Another attribute of zebrafish are their virtual transparency, which allows the observation of developmental processes using non-invasive imaging and tracking of protein/cell markers in biological and disease conditions (Spitsbergen, 2007, Blackburn et al, 2011.…”

Section: Introductionmentioning

confidence: 99%

Breeding of zebrafish in the laboratory environment for research development

Kim

Sharma

Khan

et al. 2017

Bangladesh J Pharmacol

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The zebrafish (Danio rerio) has turn out to be an excellent vertebrate organism for analyzing developmental stages, disease modeling, and screening of drug toxicities due to their minuscule, high fecundity, optical transparency and there close parallels with the genome of human beings. Although maintenance of zebrafish is relatively easy, yet it is a complex process, greatly influenced by various factors including mating behavior, day-light cycle, age, and size of fish. This visual experiment will provide an overview of zebrafish care and maintenance in the laboratory environment. Additionally, the presentation will include information essential for improving the spawning habitat by recreating breeding settings in the lab. Collectively, this experimental memorandum of zebrafish environment can serve as a mean to understand the reproducibility, efficiency of use and its welfare for future research development.

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“…5 Genomic sequencing has shown extensive homology between zebrafish and other vertebrate species (including humans), and some aspects of brain patterning, structure and function are conserved. [6][7][8][9] They are being used as model systems for various human diseases. Current dogma states that size and/or surface area is the critical physicochemical property responsible for inducing nanoparticle toxicity.…”

mentioning

confidence: 99%

Toxicity Assessment of Silver Nanoparticles in Zebrafish Embryos

Thakur¹,

Dayal²,

Pai³

et al. 2014

MGM Journal of Medical Sciences

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Genotoxic effects of silver nanoparticles (Ag-np) in a vertebrate model system were investigated.Effects and accumulation patterns of silver nanoparticles were studied using zebrafish embryos. Nanoparticles of silver were synthesized by chemical reduction of silver nitrate, using sodium borohydride as reducing agent and polyvinyl pyrolidene as a stabilizer. These nanoparticles were characterized by UV/ Vis spectrophotometer (absorption spectra), Transmission electron microscopy and were found to have the size range of 4 to 10 nm. Evaluation of cytotoxicity was carried out at various concentrations to obtain the LD 50 value. Dose dependent decrease in percent viability was observed on exposure of embryos to different concentrations of silver nanoparticles with LD 50 of 1.0 µg/ml. The results indicate that silver nanoparticles induce a dose-dependent toxicity in embryos and abrogate normal development.

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Zebrafish as a Developmental Model Organism for Pediatric Research

Cited by 168 publications

References 70 publications

Gucy2f zebrafish knockdown – a model for Gucy2d-related leber congenital amaurosis

Gucy2f zebrafish knockdown – a model for Gucy2d-related leber congenital amaurosis

Breeding of zebrafish in the laboratory environment for research development

Toxicity Assessment of Silver Nanoparticles in Zebrafish Embryos

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