This web page was produced as an assignment for Genetics 564, an undergraduate course at UW-Madison .
Model organisms_____________________________________________________________________________________________
Model organisms are species that are widely used in research due to certain experimental advantages that they possess. They are often used to obtain information about biological processes and molecular mechanisms in other organisms that are more difficult to study [1]. As examples, mice are used to model human diseases, and the mouse ear cress (known as Arabidopsis thaliana) can be used to study the cellular processes of flowering plants in general. This is possible due to homology, which means that the model organism used is evolutionarily closely related and have genes or proteins similar enough to those of the target organism.
Model organisms are species that are widely used in research due to certain experimental advantages that they possess. They are often used to obtain information about biological processes and molecular mechanisms in other organisms that are more difficult to study [1]. As examples, mice are used to model human diseases, and the mouse ear cress (known as Arabidopsis thaliana) can be used to study the cellular processes of flowering plants in general. This is possible due to homology, which means that the model organism used is evolutionarily closely related and have genes or proteins similar enough to those of the target organism.
DRD2 mutant phenotypes in model organisms____________________________________________________________________
Model organism databases were used to obtain information about DRD2 mutant phenotypes based on previously-conducted experiments. Some studies are based on mutagenesis or knockout (KO) experiments where the gene is disrupted, while others are based on gene silencing experiments using RNA interference (RNAi), which does not disrupt the gene but decreases its expression.
Model organism databases were used to obtain information about DRD2 mutant phenotypes based on previously-conducted experiments. Some studies are based on mutagenesis or knockout (KO) experiments where the gene is disrupted, while others are based on gene silencing experiments using RNA interference (RNAi), which does not disrupt the gene but decreases its expression.
Mouse Genome Informatics
A search on mouse Drd2 revealed that mice homozygous null for the gene showed 'Parkinson's disease-like symptoms, including akinetic and bradykinetic behavior'. Mice lacking only the long isoform are 'hypoactive and exhibit increased sterotypic behavior in response to dopamine agonists'. |
Rat Genome Database
Rat Drd2 mutant phenotypes include 'abnormal behavior', 'abnormal conditioned emotional response', 'decreased fear-related response' and 'increased alcohol consumption'. |
Cellular Phenotype Database
In primary screens involving silencing RNA (siRNA) experiments, it was found that HeLa cells silenced for the DRD2 genes exhibited 'increased proliferation' and 'strong decrease in rate of protein secretion'. |
Discussion__________________________________________________________________________________________________
The mutant phenotypes exhibited by mouse and rat models seem to correspond to phenotypes in humans that are associated with low DRD2 availability and certain DRD2 polymorphisms. The knockout mice, for example, showed motor defects characteristic of Parkinson's disease, which is a disease that is associated with the Taq1A polymorphism in DRD2 [2]. Drd2 knockout rats displayed increased alcohol consumption, which may be categorized as impulsive behavior.
It is also interesting to note that both knockout rats and mice exhibit decreased activity or responsiveness to dopamine agonists as in the case of mice, or to certain stimuli as in the case of rats.
The information obtained from the cellular phenotype database was not expected but interesting. However, I am unsure as to how reliable a model HeLa cells can be in research involving dopaminergic pathways, given that HeLa cells originated from tumor cells and are more widely used in research involving immunology, human physiology and carcinogenesis [3].
Generally, a good model organism to study DRD2 would be a non-human primate, since its DRD2 protein would be highly similar to human DRD2. Or ideally, DRD2 samples should be obtained directly from human subjects (Although that would have to be done with post-mortem tissue samples if it is DRD2 expression in the brain that will be studied). But behavioural studies involving Drd2 in mouse and rat models seem to have recapitulated phenotypes fairly well, which make them suitable model organisms. It should be always be kept in mind, however, that the brain structure of mice and rats are different compared to that in humans: The neocortex, for example, is smooth in rodents but more complex and highly folded in humans and non-human primates [4].
The mutant phenotypes exhibited by mouse and rat models seem to correspond to phenotypes in humans that are associated with low DRD2 availability and certain DRD2 polymorphisms. The knockout mice, for example, showed motor defects characteristic of Parkinson's disease, which is a disease that is associated with the Taq1A polymorphism in DRD2 [2]. Drd2 knockout rats displayed increased alcohol consumption, which may be categorized as impulsive behavior.
It is also interesting to note that both knockout rats and mice exhibit decreased activity or responsiveness to dopamine agonists as in the case of mice, or to certain stimuli as in the case of rats.
The information obtained from the cellular phenotype database was not expected but interesting. However, I am unsure as to how reliable a model HeLa cells can be in research involving dopaminergic pathways, given that HeLa cells originated from tumor cells and are more widely used in research involving immunology, human physiology and carcinogenesis [3].
Generally, a good model organism to study DRD2 would be a non-human primate, since its DRD2 protein would be highly similar to human DRD2. Or ideally, DRD2 samples should be obtained directly from human subjects (Although that would have to be done with post-mortem tissue samples if it is DRD2 expression in the brain that will be studied). But behavioural studies involving Drd2 in mouse and rat models seem to have recapitulated phenotypes fairly well, which make them suitable model organisms. It should be always be kept in mind, however, that the brain structure of mice and rats are different compared to that in humans: The neocortex, for example, is smooth in rodents but more complex and highly folded in humans and non-human primates [4].
References
[1] What are 'model organisms'? http://genome.wellcome.ac.uk/doc_wtd020803.html
[2] McGuire V., et al. (2011). Association of DRD2 and DRD3 polymorphisms with Parkinson's disease in a multiethnic consortium. Journal of the neurological sciences, 307(1), 22-29.
[3] https://www.google.com/url?q=https://www.crc.losrios.edu/files/onebook/Uses_of_HeLa_Cells.docx&sa=U&ei=21oWVf6KDonkoASI8IL4Cw&ved=0CAMQFjAA&client=internal-uds-cse&usg=AFQjCNGXetxeW1n5ILpq9LaTswtcP4Go8A
[4] Atlas Shows Difference between Mouse and Human Brain. http://www.alnmag.com/news/2014/04/atlas-shows-difference-between-mouse-and-human-brain
[1] What are 'model organisms'? http://genome.wellcome.ac.uk/doc_wtd020803.html
[2] McGuire V., et al. (2011). Association of DRD2 and DRD3 polymorphisms with Parkinson's disease in a multiethnic consortium. Journal of the neurological sciences, 307(1), 22-29.
[3] https://www.google.com/url?q=https://www.crc.losrios.edu/files/onebook/Uses_of_HeLa_Cells.docx&sa=U&ei=21oWVf6KDonkoASI8IL4Cw&ved=0CAMQFjAA&client=internal-uds-cse&usg=AFQjCNGXetxeW1n5ILpq9LaTswtcP4Go8A
[4] Atlas Shows Difference between Mouse and Human Brain. http://www.alnmag.com/news/2014/04/atlas-shows-difference-between-mouse-and-human-brain