This web page was produced as an assignment for Genetics 564, an undergraduate course at UW-Madison.
Model organisms
Proven how conserved both PSEN1 and PSEN1 are throughout species and organisms alike, Alzheimer's disease can be studied regularly in various model organisms. Particularly, using mammals as model organisms will prove to be essential to any neurological genetic disease research, as the nervous system is an essential component of mammalian life [1]. Referencing gene and protein homology, the phylogenetic trees, protein motifs, and domains, two model organisms that were chosen for the proposed research were the mouse and the zebrafish.
mouse- mus musculus
Mice, a common model organism for human disease research is increasingly useful for studying Alzheimer's. Being a mammal, like humans, mice have the same systems of regulation throughout their bodies, as well as experience the same type of stimulus, disease phenotypes and have relatively identical body parts and bodily functions. In addition, their relatively short reproduction rate and generation time provide a substantial amount of information regarding how a disease progresses.
Seen through homology, mice have relatively identical presenilin 1 genes and proteins, making them an ideal candidate for Alzheimer's research. Phylogenetic trees establishing the relatively recent divergence between mice and men indicate how closely presenilin 1 in mice should correspond to that of humans. |
Figure 1. Mouse as a model organism for Alzheimer's research.
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Figure 2. Previous Alzheimer's research in mice model organisms. The influence of APP on disease development is seen.
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Seen to the left is a previous Alzheimer's experiment conducted on mice model organisms. Illustrated is the influence APP has on developing disease symptoms, as only the wildtype, normal, two copy mouse developed memory deficits and early mortality [2]. Much like this study on APP, I believe that mice will also be able to model studies on PSEN1, given the similarities to humans.
In addition, the amount of research already conducted on mice model organisms not only proves how experiments can produce quality results, but also provides a large backing of research for comparison. By establishing a set of checks and balances, we can be assured that the research conducted is done in the most efficient manner. For my research, I will use mice model organisms to test against RNA interference and chemical genetics. |
zebrafish- dario rerio
Figure 3. Zebrafish as a model organism for Alzheimer's research.
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Zebrafish have a relatively conserved nervous system, similar to that of humans [3]. Almost as complex as a humans, zebrafish nervous systems rely upon the same grounds of neurotransmitters, signals, receptors, dendrites and axons to convey different neurological messages. Because of this and their relatively rapid regeneration time, zebrafish are commonly used to study neurological irregularities of other mammals--similar to that of Alzheimer's research.
Though less studied than mice, I believe zebrafish would provide an alternative approach to studying Alzheimer's. Growing more rapidly than mice while still maintaining relative consistency to both human PSEN1 and PSEN1 further conveys how zebrafish could just as easily be used to study Alzheimer's as a mouse. |
In reference to the established homology and phylogeny, zebrafish have relatively identical presenilin 1 genes and proteins to that of humans. In addition to the phylogenetic tree illustrating just how similar humans are to zebrafish, the protein domain explains how 77% of the zebrafish PSEN1 protein is identical to that of humans. That's a lot. When comparing to the reproductive capacity of zebrafish, 77% indicates that much genetic research could be completed using these model organisms over others, such as mice, that have a slightly longer generation time. Especially in a disease spanning an entire generation, such as Alzheimer's, using model organisms that can better accommodate this in less time is efficient to keeping research moving forward.
For my research, I propose using zebrafish to also test both RNA interference and chemical genetics, not only as a safeguard, but to understand how modeling Alzheimer's in zebrafish compares to that of mice or other model organisms. Hypothetically, the results should remain the same if the presenilin 1 regions are conserved; however, we will only know by actual experimentation.
For my research, I propose using zebrafish to also test both RNA interference and chemical genetics, not only as a safeguard, but to understand how modeling Alzheimer's in zebrafish compares to that of mice or other model organisms. Hypothetically, the results should remain the same if the presenilin 1 regions are conserved; however, we will only know by actual experimentation.
REFERENCES
Figure 1. http://www.redorbit.com/news/health/1112705297/stem-cells-mice-vision-100212/
Figure 2. http://www.ucsf.edu/news/2007/09/3754/circling-alzheimers-and-obesity
Figure 3. http://www.ferris.edu/htmls/colleges/artsands/biological-sciences/faculty-staff/hoerter/zebrafish-model.htm
[1] http://www.ehow.com/about_4565581_mammals-nervous-system.html
[2] http://www.ucsf.edu/news/2007/09/3754/circling-alzheimers-and-obesity
[3] Schmidt, Rebecca, Uwe Strahle, and Steffen Scholpp. "Neurogenesis in Zebrafish – from Embryo to Adult." Neural Development. N.p., 21 Feb. 2013. Web. 27 Mar. 2015. <http://www.neuraldevelopment.com/content/8/1/3>.
Figure 2. http://www.ucsf.edu/news/2007/09/3754/circling-alzheimers-and-obesity
Figure 3. http://www.ferris.edu/htmls/colleges/artsands/biological-sciences/faculty-staff/hoerter/zebrafish-model.htm
[1] http://www.ehow.com/about_4565581_mammals-nervous-system.html
[2] http://www.ucsf.edu/news/2007/09/3754/circling-alzheimers-and-obesity
[3] Schmidt, Rebecca, Uwe Strahle, and Steffen Scholpp. "Neurogenesis in Zebrafish – from Embryo to Adult." Neural Development. N.p., 21 Feb. 2013. Web. 27 Mar. 2015. <http://www.neuraldevelopment.com/content/8/1/3>.