This web page was produced as an assignment for Genetics 564, an undergraduate capstone course at UW-Madison.
What is a model organism?
A model organism is an organism used in the laboratory to study a topic that is relevant to human health. Model organisms generally have direct similarities with the human model, and the findings of these studies can be the basis of clinical studies. The advantages of using model organisms are numerous. They reproduce quickly, are inexpensive, can be studied from birth to death, and have less ethical complications than many human studies.
Which model organisms could help study allergic rhinitis and TGFB1?
There are numerous mouse models for TGFB1 as it relates to the immune system. These mice display inflammation that can be localized or more systemic. [1] Mice TGFB1 shares 90% identity with their human homolog. Mice would be a great model organism for allergic rhinitis because their immune system is very similar to ours. They have both adaptive and innate immunity, and produce inflammation in response to an allergen. Allergic rhinitis can be induced in mice quickly and easily. Mice would be very useful when studying the pathways behind TGFB1's involvement in allergic rhinitis, and one of the more obvious choices for model organisms when modeling the disease in general.
Zebra fish are a very interesting model organism for allergic rhinitis. They have a similar immune system to ours, and several inflammatory links between zebra fish and humans have been confirmed. [2] However, they have gills which allow oxygen from the water to be absorbed into their circulatory system. They do not have lungs, and do not have nasal tissue that is very similar to ours. Because of these dissimilarities, you may think that zebra fish would not be a good model organism for allergic rhinitis. However, we must remember that at the root of the disease is the inflammation.
The key immune cell when discussing inflammation is the neutrophil. [2] In developing zebra fish embryos, neutrophils can be visualized. This allows scientists to preform drug screens on the developing fish. Because the target animal here is going to be the adult zebra fish, it would also be useful to track the neutrophils after the embryonic stage. Conveniently, there is a transgenic model of neutrophilic inflammation, which expresses GFP under a neutrophil specific marker. [3] Certain anti-inflammatory drugs, specifically ones that target TGFB1, are an exciting angle on allergy treatment. The anti-inflammatory drug could be easily tested in zebra fish. [2]
Additionally, a common chemical called Polysorbate 80 with hydrogen peroxide impurities can be used to induce an allergic response in the fish. [4] A fish that is having a systemic inflammatory response will be easy to pick out, because the fish will look puffy. We can then use this allergic model to test a drug and determine whether that drug can decrease the inflammatory response due to TGFB1.
The key immune cell when discussing inflammation is the neutrophil. [2] In developing zebra fish embryos, neutrophils can be visualized. This allows scientists to preform drug screens on the developing fish. Because the target animal here is going to be the adult zebra fish, it would also be useful to track the neutrophils after the embryonic stage. Conveniently, there is a transgenic model of neutrophilic inflammation, which expresses GFP under a neutrophil specific marker. [3] Certain anti-inflammatory drugs, specifically ones that target TGFB1, are an exciting angle on allergy treatment. The anti-inflammatory drug could be easily tested in zebra fish. [2]
Additionally, a common chemical called Polysorbate 80 with hydrogen peroxide impurities can be used to induce an allergic response in the fish. [4] A fish that is having a systemic inflammatory response will be easy to pick out, because the fish will look puffy. We can then use this allergic model to test a drug and determine whether that drug can decrease the inflammatory response due to TGFB1.
Analysis
Model organisms will make studying allergic rhinitis and TGFB a lot more practical. There is extensive research on this gene and how it interacts with many systems in the body, and this is mainly through the help of model organisms. In this study specifically, model organisms will be helpful because studying allergic rhinitis human patients may be highly variable. We can use our knowledge of homologous genes between species to infer and understand the relationship of TGFB1 on the body, the immune system, and allergic rhinitis.
This study will use zebra fish. It's the most practical choice for understanding the effects of Losartan on allergic rhinitis as it relates to TGFB1.
This study will use zebra fish. It's the most practical choice for understanding the effects of Losartan on allergic rhinitis as it relates to TGFB1.
References
[1] Blake JA, Eppig JT, Kadin JA, Richardson JE, Smith CL, Bult CJ, and the Mouse Genome Database Group. 2017. Mouse Genome Database (MGD)-2017: community knowledge resource for the laboratory mouse. Nucl. Acids Res. 2017 Jan. 4;45 (D1): D723-D729.
[2] Loynes, C. A., Martin, J. S., Robertson, A., Trushell, D. M., Ingham, P. W., Whyte, M. K., & Renshaw, S. A. (2010). Pivotal Advance: Pharmacological manipulation of inflammation resolution during spontaneously resolving tissue neutrophilia in the zebrafish. Journal of leukocyte biology, 87(2), 203-212. Chicago
[3] Renshaw et al. (2006). A transgenic zebrafish model of neutrophilic inflammation. American Society of Hematology. 108:3976-3978. https://doi.org/10.1182/blood-2006-05-024075
[4] Yang et al. (2014). Tween-80 and impurity induce anaphylactoid reaction in zebra fish. Journal of applied Toxicology. 35,3:295-301. 10.1002/jat.3069
Images
[1] https://elifesciences.org/content/4/e06956
[2] https://www.thermofisher.com/blog/food/can-feedstocks-trigger-allergic-reaction-in-humans-up-the-food-chain/
[3] https://www.dreamstime.com/stock-photo-wood-mouse-front-white-background-walk-image60160268
[2] Loynes, C. A., Martin, J. S., Robertson, A., Trushell, D. M., Ingham, P. W., Whyte, M. K., & Renshaw, S. A. (2010). Pivotal Advance: Pharmacological manipulation of inflammation resolution during spontaneously resolving tissue neutrophilia in the zebrafish. Journal of leukocyte biology, 87(2), 203-212. Chicago
[3] Renshaw et al. (2006). A transgenic zebrafish model of neutrophilic inflammation. American Society of Hematology. 108:3976-3978. https://doi.org/10.1182/blood-2006-05-024075
[4] Yang et al. (2014). Tween-80 and impurity induce anaphylactoid reaction in zebra fish. Journal of applied Toxicology. 35,3:295-301. 10.1002/jat.3069
Images
[1] https://elifesciences.org/content/4/e06956
[2] https://www.thermofisher.com/blog/food/can-feedstocks-trigger-allergic-reaction-in-humans-up-the-food-chain/
[3] https://www.dreamstime.com/stock-photo-wood-mouse-front-white-background-walk-image60160268