Zebrafish Myelodysplastic Syndrome Models

Myelodysplastic syndromes (MDS) are particularly challenging to accurately model in animals due to their heterogeneity. The zebrafish Danio rerio has been established as a reliable method for modeling human leukemia in vivo. It is relatively easy to rear, fecundity, genetic manipulation and high-throughput screening capabilities compared to mouse models. Furthermore, most core regulators of hematopoiesis are evolutionarily conserved between teleost fish such as zebrafish and mammals, so the findings in zebrafish can be directly translated to mouse and human systems.

According to the recently completed and updated annotation of the zebrafish genome, approximately 70% of protein-coding genes in humans have at least one ortholog in zebrafish, and 84% of disease-related genes have zebrafish equivalents. This degree of homology further demonstrates the potential utility of zebrafish in defining key regulators and underlying genetic causes of malignancy. In conclusion, the zebrafish model offers many advantages for studying the mechanisms of normal and malignant myelopoiesis. From embryonic development to adulthood, the fate determination, differentiation and maturation of myeloid cells are highly similar. Therefore, the study of bone marrow development in zebrafish contributes not only to understanding embryonic development but also to understanding adult bone marrow malignancies.

Fig. 1 tet2^m/m zebrafish develop premyelodysplasia at 11 months of age.

Our Zebrafish MDS Models

Creative Biogene has more than ten years of experience in zebrafish disease research, and we have a wealth of zebrafish models and genome editing platforms. We can provide a variety of transgenic zebrafish models such as tet2 mutant zebrafish lines, asxl1 mutant zebrafish lines, human NUP98-HOXA9 transgenic zebrafish lines, and crs mutant zebrafish lines. Among them, the tet2 mutant zebrafish line exhibited normal embryonic and larval hematopoiesis, but developed progressive clonal myelodysplasia with age, eventually developing MDS at 24 months of age with dysplasia of myeloid progenitors and Anemia with abnormal circulating red blood cells. Human NUP98-HOXA9 transgenic zebrafish with disrupted hematopoiesis and enhanced spi1+ myeloid precursors develop myeloproliferative tumors between 19 and 23 months of age. Zebrafish crs mutants exhibit phenotypes consistent with MDS, including multilineage cytopenias including reduced hbbe3+ and mpo+ cells, disruption of Gata1+ precursors, and cell dysplasia.

Creative Biogene aims to provide a reliable zebrafish model for studying MDS, and our tools can provide a unique opportunity for high-throughput in vivo chemical modifier screening to help you identify novel therapeutics specific to MDS.

Advantages

• High-throughput gene and drug screening
• Rapidly perform reverse and forward genetic screening
• Observe different cells and tissues in real time
• Track labeled cancer cells in in vivo imaging analysis

References

1. Rasighaemi P, et al. Zebrafish as a model for leukemia and other hematopoietic disorders. J Hematol Oncol. 2015, 8:29.
2. Gjini E, et al. A zebrafish model of myelodysplastic syndrome produced through tet2 genomic editing. Mol Cell Biol. 2015, 35(5):789-804.

For research use only. Not intended for any clinical use.