This web page was produced as an assignment for Genetics 677 an undergraduate course at UW-Madison
What is RNAi?RNAi is called RNA interference. It is a molecular tool that can be used in some model organisms. How it works is that it will cause a gene to become silent and not express as if it had been mutated and became not functional [1]. This is done through the injection of double stranded RNA into an organism which causes the RNA produced from the DNA to be destroyed and therefore leads to the knock out of expression of the gene [1]. It can be used in some model organisms to study the affect of loosing certain proteins or seeing what symptoms a gene mutation can cause.
To better understand the process of RNAi, watch the video to the right. It explains RNAi in much greater depth and provides nice visuals to understand how this process works. |
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BBS1 and RNAi
The pheotypes or affects of RNAi were gathered from different databases: Flybase (fuit fly), Flight (fruit fly), Mouse Genome Informatics (mouse), Wormbase (C. elegans) and ZFIN (zebrafish). There are other databases that can be used to look at other pheotypes of RNAi in different organisms however these organisms did not have a BBS1 homolog.
Fruit Fly
Although a BBS1 homolog exists in flies, not much had been studied about this gene in this organism using this molecular tool. Phenotypes included:
- Lethality
- Average Survival
- Decreased Flag-Mag transportation
Mouse
More studies had been done on this gene using this molecular tool in mice versus that in fly. There were a couple more phenotypes that greatly resemble the symptoms that Bardet-Biedl Patients experience. Phenotypes included:
- Homozygous null mice display partial embryonic lethality
- Low body weight before weaning
- Obesity after weaning
- Retinal degeneration
- Abnormal olfactory epithelium and neurons.
C. elegans
As with the mice, not many RNAi studies have been performed on this organism to study the homolog of BBS1. However, some studies have been done and some interesting phenotypes were found in this organism. Phenotypes included:
- amphid phasmid morphology variant
- associative learning variant
- cilia morphology variant
- greater fat accumulation [2]
Zebrafish
Although a homolog of BBS1 is found in Zebrafish, no RNAi studies had been done on this gene in this organism.
Analysis and Discussion
RNAi is a really useful tool to look at the phenotypes that can emerge from the loss of a gene. There were not many RNAi studies done on the model organisms that had the BBS1 gene homolog. The ones that were did have interesting phenotypes associated with the loss of this gene. The mice had very similar phenotypes as those symptoms found in Bardet-Biedl Syndrome. There was the greater accumulation of fat and retinal damage which points to the mouse being a good model organism in which to perform studies of those symptoms. C. elegans, after some researching in primary articles, was found to have greater fat accumulation also. This is very interesting because C. elegans are not mammals as mice are and therefore it is more surprising to see a similar phenotype as that in humans. However, C. elegans have a very similar fat regulatory system as humans indicating that this would be a good model organism in which to study the symptom of obesity found in Bardet-Biedl patients.
See future directions how C. elegans could be utilized.
See future directions how C. elegans could be utilized.
References:
[Banner Photo]"NDM-1" NDM-1. Retrieved 12 March 2013 from http://www.personal.psu.edu/czc5161/blogs/testing/references.html.
[1] RNA Interference. Nature Reviews. Retrieved May 15, 2013 from http://www.nature.com/nrg/multimedia/rnai/index.html
[2] Lee, B.H. et al. (2011). Hyperactive Neuroendocrine Secretion Cuases Size, Feeding, and Metabolic Defects of C. elegans Bardet-Biedl Syndrome Mutants. PLOS biology, 9(12). doi:10.137/journal.pbio.1001219.
[Banner Photo]"NDM-1" NDM-1. Retrieved 12 March 2013 from http://www.personal.psu.edu/czc5161/blogs/testing/references.html.
[1] RNA Interference. Nature Reviews. Retrieved May 15, 2013 from http://www.nature.com/nrg/multimedia/rnai/index.html
[2] Lee, B.H. et al. (2011). Hyperactive Neuroendocrine Secretion Cuases Size, Feeding, and Metabolic Defects of C. elegans Bardet-Biedl Syndrome Mutants. PLOS biology, 9(12). doi:10.137/journal.pbio.1001219.