Zebrafish Mutation-induced inflammation Models

Dysregulation of the inflammatory response in humans leads to various inflammatory diseases, such as asthma and rheumatoid arthritis. Innate branches of the immune system, including macrophage and neutrophil function, play key roles in all inflammatory diseases. Because the zebrafish is a genetically tractable vertebrate suitable for small molecule screening, it has emerged as a powerful model system for studying inflammatory mechanisms in humans.

The innate and adaptive immune systems are present in zebrafish, so zebrafish can be used as a tool to examine the role of immune cells in normal development and the pathogenesis of disease states. Recent advances in transgenic zebrafish can further elucidate these immune responses, in which specific cell lineages including lymphocytes, macrophages and neutrophils are labeled with fluorescent proteins such as green fluorescent protein. These transgenic zebrafish can be used to provide high-resolution analysis of leukocyte development and trafficking and provide important insights into the evolution of inflammatory responses.

Fig 2. A transgenic zebrafish model of neutrophilic inflammation.

Our Zebrafish Mutation-induced inflammation Models

Zebrafish Hai1a Mutation Models

Creative Biogene rapidly generated hai1a mutant zebrafish by large-scale insertional mutagenesis. These mutant zebrafish larvae expressed the neutrophil-specific zebrafish myeloperoxidase (MPO; also known as Mpx) gene and exhibited similar In human psoriasis phenotypes, basal keratinocytes in the epidermis lose their regular polygonal shape, make close contact with adjacent cells, form aggregates, and show enhanced apoptosis. In this model we established, hai1 mutant zebrafish embryos exhibited inflammation in the hyperproliferative regions of the epidermis, mainly manifested by abnormal distribution of MPO-expressing cells and infiltration of neutrophils into zebrafish fins. We utilized time-lapse fluorescence microscopy of optically clear mutant embryos expressing GFP in neutrophils to track the migration of individual neutrophils within the inflamed epithelium. Our hai1a mutant zebrafish model provides important support as a novel model system for studying chronic inflammation and displaying high-resolution immune responses in real time.

The main inflammatory response: Epidermal defects; leukocyte accumulation; enhanced keratinocyte apoptosis; upregulation of inflammatory genes

Zebrafish Cdipt Mutation Models

For liver defects, Creative Biogene offers mutants inserted in the cdp-diacylglycerol-inositol-phosphatidyltransferase (cdipt) gene. Our Cdipt mutant larvae exhibit chronic endoplasmic reticulum stress and develop hepatic steatosis at around 5 dpf, similar to features of human nonalcoholic fatty liver disease. Additionally, our cdipt mutants exhibit a pathological phenotype similar to IBD in the gastrointestinal tract. In our zebrafish cdipt mutants, deficiency of phosphatidylinositol (PtdIns) leads to ER stress-mediated cytopathology in intestinal epithelial cells, including vacuolation, microvillus atrophy, and impaired proliferation, which subsequently leads to Reduced mucus secretion, goblet cell apoptosis, autophagy, and bacterial overgrowth. Ultimately, the models will develop an inflammatory response, mainly reflected in the infiltration of macrophages and neutrophils into the gut.

Inflammatory responses: intestinal damage; reduced mucus secretion; infiltration of macrophages and neutrophils; spheroid apoptosis; impaired proliferation; endoplasmic reticulum stress; upregulation of inflammatory genes

Our Advantages

• Transgenic models available
• Provides automated high-throughput drug screening
• Easily monitor the progression of the disease

Creative Biogene not only provides models of mutation-induced inflammation, but can also design experiments and provide experimental results according to your research goals. If you would like to learn more about zebrafish models, please feel free to contact us.

References

1. Xie Y, Meijer AH, Schaaf MJM. Modeling Inflammation in Zebrafish for the Development of Anti-inflammatory Drugs. Front Cell Dev Biol. 2021, 8:620984.
2. Mathias JR, et al. Live imaging of chronic inflammation caused by mutation of zebrafish Hai1. J Cell Sci. 2007, 120(Pt 19):3372-3383.
3. Renshaw SA, et al. A transgenic zebrafish model of neutrophilic inflammation. Blood. 2006, 108(13):3976-3978.

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