Effectiveness of zebrafish models in understanding human diseases-A review of models

Abstract

Understanding the detailed mechanism behind every human disease, disorder, defect, and deficiency is a daunting task concerning the clinical diagnostic tools for patients. Hence, a closely resembling living or simulated model is of paramount interest for the development and testing of a probable novel drug for rectifying the conditions pertaining to the various ailments. The animal model that can be easily genetically manipulated to suit the study of the therapeutic motive is an indispensable asset and within the last few decades, the zebrafish models have proven their effectiveness by becoming such potent human disease models with their use being extended to various avenues of research to understand the underlying mechanisms of the diseases. As zebrafish are explored as model animals in understanding the molecular basis and genetics of many diseases owing to the 70% genetic homology between the human and zebrafish genes; new and fascinating facts about the diseases are being surfaced, establishing it as a very powerful tool for upcoming research. These prospective research areas can be explored in the near future using zebrafish as a model. In this review, the effectiveness of the zebrafish as an animal model against several human diseases such as osteoporosis, atrial fibrillation, Noonan syndrome, leukemia, autism spectrum disorders, etc. has been discussed.

Keywords: Experimental disease models; Human disease models; Teleost disease model; Zebrafish model; Zebrafish translational research.

Graphical abstract

Fig. 1

The figure represents the progressive use of zebrafish disease models over the years from data that has been curated from [A] Scopus and [B] PubMed databases showing few of the broadly categorized fields where the zebrafish models are of great value.

Fig. 2

This figure shows the schematic representations of [A] The life cycle of zebrafish which make it one of the most lucrative propositions as a model organism for diseases, [B] the comparison of the human and zebrafish genome with the help of Cinteny web server (http://cinteny.cchmc.org/) where the chromosomes are segregated and arranged with a particular color code which encodes for various syntenic regions between the two and [C] the mechanisms through which stable zebrafish mutant lines are created in the laboratory.

Fig. 3

The figure shows two models of zebrafish, used effectively to treat bone diseases. [A] The zebrafish having the atp6V1h mutation (±) shows a curved phenotype when compared to its wild-type counterpart (+/+) due to the curvature of the spine. [B] Shows the scan of wild-type zebrafish alongside the longitudinal cut of the vertebral body while [C] represents the scan of the chi/+ mutant showing deformities of the fins and ribs along with heterogeneous skull mineralization while also demonstrating an odd geometry and mineralization of hard tissues. Adapted with permission from references [26,30].

Fig. 4

The figure shows zebrafish models used in treating cardiac-related issues. [A-B] Shows the morphology of the [A] 5-week-old control zebrafish and the [B] zebrafish with a mutated plakoglobin demonstrating arrhythmogenic cardiomyopathy (scaled to 1 mm); [C-D] Represents the cardiac function analysis performed in the control and kif20a morphants where [C] the heart rate is compared between the control and the kif20a morphants at 3 days post fertilization (dpf) and 4 dpf resulting in an appreciable rise in the heart rate at 4 dpf associated with progressive cardiac failure [D] A significant fractional shortening can be observed at 4dpf in both atrium and ventricle in morphants of the morphants when compared to the control but based on more outliers and systolic failure could be predicted; [E-H] Represents the control and kif20a mutant models where it can be observed that [G-H] pronounced cardiac edema (denoted by the red arrows) can be observed in morphants at both 3 and 4 dpf while cerebral edema in morphants (denoted by *) could only be seen at 3 dpf which was not present in the [E-F] controls at 3 and 4 dpf. Adapted with permission from references [46,52]

Fig. 5

This figure demonstrates the zebrafish models utilized in understanding human diseases. [A-B] Shows the zebrafish model, CG1 tp53^del/del used for studying spontaneous and induced tumors; [C-D] Even though the wild-type zebrafish larva shows a normal morphology, the ctns−/− mutant shows deformities such as growth retardation [D, upper] denoted by the bigger yolk, [D, middle and lower] bent head, and bulging eyes with mild and severe deformities; [E-F] In comparison to the [E] control morphant (Co.Mo.), [F]ELMO1 crispant (ELMO1 CRISPR) showed an enlarged glomerulus (depicted by the white arrowhead) and shortened pronephric neck (denoted by white asterisk) suggesting an adverse effect of hyperglycemia upon the pronephric structure of zebrafishes; [G] The effectiveness of the WASp1^−/− model in the timed recruitment of neutrophils when compared to wild-type zebrafish larvae and [H] the schematic diagram of the WASp1^−/− model; [I–K] Shows the various models and experimental results obtained for studies related to blood disease models. The different phenotypes of rps19 homozygous mutants at different timed stages – [I] 24hpf, [J] 48hpf, and [K] 3dpf are shown. Adapted with permission from references [68,69,77,89,95].