A model organism is a non-human species that is used to conduct scientific experiments. A model organism are usually easy to maintain, manipulate and show similar phenotypes to humans when exposed to treatments [1]. Choosing a model organism is not a trivial task. Typically, a model organism should be widely-studied and well characterized before being chosen. Specifically in genetic experimentation, the model organisms being used should exhibit similar phenotypes to humans when homologous genes are mutated [2]. Additionally, it is ideal to choose a model organism that breed in large numbers so that large enough sample sizes can be generated to make evidence-based conclusions.
Common Model Organisms
Zebrafish
The zebrafish (Danio rerio) is a fantastic model to study genetic disorders. They can be bred easily and rapidly, and their partially transparent bodies make it great for readily observing phenotypes that occur in the nervous system. Additionally, their central nervous system shares several similarities to that of humans. |
The Ts65Dn Mouse Model
In general, using the common mouse (Mus musculus) to study genetic diseases is also useful. This is because mutations in homologous genes in mice often cause phenotypes that are similar to the disease phenotypes in humans [3]. The Ts65Dn mouse strain is especially useful to study DYRK1A overexpression because these mice are trisomic for several of the orthologs that are overexpressed in humans with trisomy chromosome 21 [2]. These mice also show neurological development and cognitive deficits that are normally seen in human patients with Down syndrome.
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Conclusion
For the study of DYRK1A, and its role in the development of Down syndrome, zebrafish (Danio rerio) will be chosen as the model organism. Zebrafish will be an ideal model organism because the transparent nervous system allows for simple observation of neural cell proliferation. Additionally, the zebrafish nervous system is well-known to be very similar to the nervous system in humans. With further research in the DYRK1A protein homology, the protein domains present in humans are well conserved in zebrafish making it a suitable model to observe the connection between the levels of DYRK1A and neural cell proliferation.
References:
1. https://www.yourgenome.org/facts/what-are-model-organisms
2. Olson L.E., et al. Down syndrome mouse models Ts65Dn, Ts1Cje, and Ms1Cje/Ts65Dn exhibit variable severity of cerebellar phenotypes. Dev. Dyn. 2004;230:581–589.
3. https://www.nature.com/scitable/topicpage/the-use-of-animal-models-in-studying-855/
3. Nguyen, Thu Lan et al. “Correction of cognitive deficits in mouse models of Down syndrome by a pharmacological inhibitor of DYRK1A.” Disease models & mechanisms vol. 11,9 dmm035634. 27 Sep. 2018. Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5125364/?report=classic
4. Liu, Y., Lin, Z., Liu, M., Wang, H., & Sun, H. (2017). Overexpression of DYRK1A, a Down Syndrome Candidate gene, Impairs Primordial Germ Cells Maintenance and Migration in zebrafish. Scientific reports, 7(1), 15313. Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5681638
Image References:
Header: https://iiif.elifesciences.org/journal-cms/collection%2F2015-09%2F8de90445-model-organisms-elife-collections.png/full/full/0/default.jpg
Image 1: https://www.google.com/url?sa=i&url=https%3A%2F%2Fpowersscientific.com%2Feffects-of-lighting-on-zebrafish%2F&psig=AOvVaw3prTyMejHnFexEWOlRk5xN&ust=1589217530367000&source=images&cd=vfe&ved=0CAIQjRxqFwoTCIiv3-XmqekCFQAAAAAdAAAAABAI
Image 2: https://www.jax.org/~/media/JaxWeb/images/jax-mice-and-services/mice/datasheets/005252
2. Olson L.E., et al. Down syndrome mouse models Ts65Dn, Ts1Cje, and Ms1Cje/Ts65Dn exhibit variable severity of cerebellar phenotypes. Dev. Dyn. 2004;230:581–589.
3. https://www.nature.com/scitable/topicpage/the-use-of-animal-models-in-studying-855/
3. Nguyen, Thu Lan et al. “Correction of cognitive deficits in mouse models of Down syndrome by a pharmacological inhibitor of DYRK1A.” Disease models & mechanisms vol. 11,9 dmm035634. 27 Sep. 2018. Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5125364/?report=classic
4. Liu, Y., Lin, Z., Liu, M., Wang, H., & Sun, H. (2017). Overexpression of DYRK1A, a Down Syndrome Candidate gene, Impairs Primordial Germ Cells Maintenance and Migration in zebrafish. Scientific reports, 7(1), 15313. Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5681638
Image References:
Header: https://iiif.elifesciences.org/journal-cms/collection%2F2015-09%2F8de90445-model-organisms-elife-collections.png/full/full/0/default.jpg
Image 1: https://www.google.com/url?sa=i&url=https%3A%2F%2Fpowersscientific.com%2Feffects-of-lighting-on-zebrafish%2F&psig=AOvVaw3prTyMejHnFexEWOlRk5xN&ust=1589217530367000&source=images&cd=vfe&ved=0CAIQjRxqFwoTCIiv3-XmqekCFQAAAAAdAAAAABAI
Image 2: https://www.jax.org/~/media/JaxWeb/images/jax-mice-and-services/mice/datasheets/005252
This web page was produced as an assignment for Genetics 564, an undergraduate capstone course at UW-Madison.