Zebrafish Models of Human Disease: Gaining Insight into Human Disease at ZFIN

Abstract

The Zebrafish Model Organism Database (ZFIN; https://zfin.org) is the central resource for genetic, genomic, and phenotypic data for zebrafish (Danio rerio) research. ZFIN continuously assesses trends in zebrafish research, adding new data types and providing data repositories and tools that members of the research community can use to navigate data. The many research advantages and flexibility of manipulation of zebrafish have made them an increasingly attractive animal to model and study human disease.To facilitate disease-related research, ZFIN developed support to provide human disease information as well as annotation of zebrafish models of human disease. Human disease term pages at ZFIN provide information about disease names, synonyms, and references to other databases as well as a list of publications reporting studies of human diseases in which zebrafish were used. Zebrafish orthologs of human genes that are implicated in human disease etiology are routinely studied to provide an understanding of the molecular basis of disease. Therefore, a list of human genes involved in the disease with their corresponding zebrafish ortholog is displayed on the disease page, with links to additional information regarding the genes and existing mutations. Studying human disease often requires the use of models that recapitulate some or all of the pathologies observed in human diseases. Access to information regarding existing and published models can be critical, because they provide a tractable way to gain insight into the phenotypic outcomes of the disease. ZFIN annotates zebrafish models of human disease and supports retrieval of these published models by listing zebrafish models on the disease term page as well as by providing search interfaces and data download files to access the data. The improvements ZFIN has made to annotate, display, and search data related to human disease, especially zebrafish models for disease and disease-associated gene information, should be helpful to researchers and clinicians considering the use of zebrafish to study human disease.

Knockdown of hspg2 is associated with mandibular jaw joint fusion and neural crest cell dysfunction in zebrafish

“…Zebra sh are remarkably easy to manipulate genetically and have been used with great success in genetic studies. The zebra sh genome shares a high degree of genetic similarity with humans and thus, provides a manner in which to understand gene function and mechanisms (30). 70% of human genes have one zebra sh ortholog and 82% of the genes associated with disease also have at least one zebra sh ortholog (56).…”

“…Apart from general advantages like a high fecundity rate, extrauterine development, and quick maturation, the zebra sh is an ideal organism to study craniofacial development due to the relative simplicity of the cartilaginous structures of the head and face, all of which are readily visible with stains like Alcian blue (29,30). Additionally, the zebra sh shares a high degree of genetic similarity to humans and successful studies have been performed using genetically manipulated sh (30). Thus, we performed transient knockdown of zebra sh hspg2 to determine the CNCC defects present during craniofacial development.…”

Circulating tumor cells exit circulation while maintaining multicellularity augmenting metastatic potential

“…The limitations of current imaging technologies prevent the intravital imaging of tumor cell extravasation in real time in humans, but the zebrafish offers a biologically relevant system to deeply study key aspects of this process (Bradford et al, 2017;Ablain and Zon, 2013;Gore et al, 2012;Chávez et al, 2016). Taking advantage of a model that allows for the visualization of tumor cells extravasation in real time, and a unique method to isolate extravasation-participating tumor and endothelial cells, we show that CTCs possess the ability to extravasate through AP by triggering the activation of vascular remodeling in endothelial cells.…”

Antibodies, Nanobodies, or Aptamers—Which Is Best for Deciphering the Proteomes of Non-Model Species?

“…Though the zebrafish has only recently gained popularity as a model organism, we have already made vital discoveries using zebrafish to understand developmental pathways, disease progression, and therapeutic strategies for diseases and disorders [3]. While there are a plethora of reasons why zebrafish serve as an ideal model for investigating immune cell development and disease progression, such as their transparent embryonic and larval developmental stages (reviewed in [4]), the primary reason for their widespread use is that their genome has been sequenced, making it easier to make significant comparisons between the genome and the proteome.…”