Hooked! Modeling human disease in zebrafish

Santoriello, Cristina; Zon, Leonard I.

doi:10.1172/jci60434

Cited by 439 publications

(347 citation statements)

References 109 publications

Supporting

Mentioning

326

Contrasting

Unclassified

Order By: Relevance

“…For example, aminoglycosides (gentamicin and paromycin) have shown remarkable therapeutic efficacy in the zebrafish mutants (lamb and pax 2). 112 These mutants recapitulate coloboma formation, which can be characterized by a triangular eyelid defect as a result of unsuccessful closure of choroid fissure during early morphogenesis of the eye. 64 These findings reveal the potential of aminoglycosides in the treatment of human coloboma.…”

Section: Ophthalmological Drug Discovery and Development In Zebrafishmentioning

confidence: 97%

“…64 These findings reveal the potential of aminoglycosides in the treatment of human coloboma. 112 Furthermore, the zebrafish model has established itself as a prominent model system for hypoxia-induced retinopathy. 87 These hypoxic zebrafish models have been utilized to test oral anti-angiogenesis inhibitors (anti-VEGF agents), such as sunitinib and zm323881.…”

Section: Ophthalmological Drug Discovery and Development In Zebrafishmentioning

confidence: 99%

See 1 more Smart Citation

Zebrafish—on the move towards ophthalmological research

Chhetri

Jacobson

Gueven

2014

Eye

135

114

View full text Add to dashboard Cite

Millions of people are affected by visual impairment and blindness globally, and the prevalence of vision loss is likely to increase as we are living longer. However, many ocular diseases remain poorly controlled due to lack of proper understanding of the pathogenesis and the corresponding lack of effective therapies. Consequently, there is a major need for animal models that closely mirror the human eye pathology and at the same time allow higher-throughput drug screening approaches. In this context, zebrafish as an animal model organism not only address these needs but can in many respects reflect the human situation better than the current rodent models. Over the past decade, zebrafish have become an established model to study a variety of human diseases and are more recently becoming a valuable tool for the study of human ophthalmological disorders. Many human ocular diseases such as cataract, glaucoma, diabetic retinopathy, and age-related macular degeneration have already been modelled in zebrafish. In addition, zebrafish have become an attractive model for pre-clinical drug toxicity testing and are now increasingly used by scientists worldwide for the discovery of novel treatment approaches. This review presents the advantages and uses of zebrafish for ophthalmological research.

show abstract

Section: Ophthalmological Drug Discovery and Development In Zebrafishmentioning

confidence: 97%

Section: Ophthalmological Drug Discovery and Development In Zebrafishmentioning

confidence: 99%

Zebrafish—on the move towards ophthalmological research

Chhetri

Jacobson

Gueven

2014

Eye

135

114

View full text Add to dashboard Cite

show abstract

“…D'autres avantages du poisson zèbre incluent son développement rapide, sa facilité de manipulation et sa transparence. Ces propriétés uniques en font un puissant modèle vertébré pour le traçage génétique et les analyses in vivo à l'échelle de la cellule [6]. La possibilité d'utiliser des morpholinos (voir Glossaire) pour manipuler génétiquement le danio représente également un outil important pour identifier rapidement des gènes potentiellement impliqués dans la pathologie.…”

Section: Le Poisson Zèbre Un Modèle D'étude Des Dystrophies Musculaiunclassified

Le poisson zèbre

Ryckebüsch

2015

Med Sci (Paris)

View full text Add to dashboard Cite

> Dans le but de mieux comprendre la complexité des dystrophies musculaires congénitales (DMC) et de développer des stratégies pour les traiter, il est important d'établir de nouveaux modèles de ces maladies. En raison de ses nombreuses caractéristiques, le poisson zèbre est récemment devenu un modèle de choix dans l'étude des DMC. La modélisation de certaines de ces dystrophies dans ce modèle vertébré permet en effet d'obtenir un phénotype plus proche de la maladie humaine que le modèle murin. Ces dernières années, grâce à des moyens techniques innovants, il est devenu possible de cribler rapidement et à grande échelle les pathologies musculaires dans ce modèle. Par ailleurs, les nouvelles techniques de modification du génome du poisson ouvrent la voie vers la création de nouveaux modèles pour analyser les DMC. Cette revue discute des qualités majeures du poisson zèbre pour l'étude des DMC et présente les principaux modèles de dystrophies obtenus dans ce modèle. < chez l'homme, afin de caractériser de nouveaux gènes d'intérêt, de comprendre l'évolution de la maladie et de développer de nouvelles thérapies. Le modèle vertébré du poisson zèbre (Danio rerio) a montré son intérêt dans ces avancées [51] 1 . Dans cette revue, nous décrirons les différents aspects des DMC. Nous énumérerons ensuite les moyens mis en oeuvre pour analyser ces pathologies dans le modèle de choix que représente le poisson zèbre. Nous discuterons enfin de la pertinence de certaines études réalisées avec ce modèle, offrant un intérêt particulier pour la compréhension des DMC. Les dystrophies musculaires congénitalesL'hétérogénéité des DMC est illustrée par la variabilité de leurs signes cliniques, mais également par l'âge d'apparition des premiers symptômes. L'étiologie de ces maladies est diverse et complexe. Des mutations différentes d'un même gène peuvent entraîner des manifestations cliniques très variées, et cela au sein d'une même famille ; à l'inverse, des symptômes similaires peuvent résulter d'altérations génomiques distinctes [3]. Outre la classification clinique, les DMC sont aussi classées selon les déficits moléculaires qui les caractérisent (dystroglycanopathies, laminopathies, etc.)

show abstract

“…Principles of energy expenditure and metabolism are evolutionarily conserved in metazoans (Schlegel & Stainier 2007). In addition, zebrafish larvae at 4 days post fertilization (dpf) have developed many functional organs (Elo et al 2007), with the advantages inherent to the zebrafish larvae system as presented in many review papers (Lieschke & Currie 2007, Ali et al 2011, Liu & Leach 2011, Meijer & Spaink 2011, Santoriello & Zon 2012, Driessen et al 2013, Seth et al 2013. We therefore set out to develop a non-obese zebrafish model for the study of insulin metabolism and its associated disorders.…”

Section: Introductionmentioning

confidence: 99%

Hyperinsulinemia induces insulin resistance and immune suppression via Ptpn6/Shp1 in zebrafish

Marín-Juez¹,

Jong-Raadsen²,

Yang³

et al. 2014

Journal of Endocrinology

View full text Add to dashboard Cite

Type 2 diabetes, obesity, and metabolic syndrome are pathologies where insulin resistance plays a central role, and that affect a large population worldwide. These pathologies are usually associated with a dysregulation of insulin secretion leading to a chronic exposure of the tissues to high insulin levels (i.e. hyperinsulinemia), which diminishes the concentration of key downstream elements, causing insulin resistance. The complexity of the study of insulin resistance arises from the heterogeneity of the metabolic states where it is observed. To contribute to the understanding of the mechanisms triggering insulin resistance, we have developed a zebrafish model to study insulin metabolism and its associated disorders. Zebrafish larvae appeared to be sensitive to human recombinant insulin, becoming insulin-resistant when exposed to a high dose of the hormone. Moreover RNA-seq-based transcriptomic profiling of these larvae revealed a strong downregulation of a number of immune-relevant genes as a consequence of the exposure to hyperinsulinemia. Interestingly, as an exception, the negative immune modulator protein tyrosine phosphatase nonreceptor type 6 (ptpn6) appeared to be upregulated in insulin-resistant larvae. Knockdown of ptpn6 was found to counteract the observed downregulation of the immune system and insulin signaling pathway caused by hyperinsulinemia. These results indicate that ptpn6 is a mediator of the metabolic switch between insulin-sensitive and insulin-resistant states. Our zebrafish model for hyperinsulinemia has therefore demonstrated its suitability for discovery of novel regulators of insulin resistance. In addition, our data will be very useful in further studies of the function of immunological determinants in a non-obese model system.

show abstract

Hooked! Modeling human disease in zebrafish

Cited by 439 publications

References 109 publications

Zebrafish—on the move towards ophthalmological research

Zebrafish—on the move towards ophthalmological research

Le poisson zèbre

Hyperinsulinemia induces insulin resistance and immune suppression via Ptpn6/Shp1 in zebrafish

Contact Info

Product

Resources

About