This web page was produced as an assignment for Genetics 564, an undergraduate course at UW-Madison
How can we study tubby?
Since performing experiments on humans is ethically unacceptable, model organisms are typically used to better understand human diseases. An ideal model organism is closely related to humans as indicated by homology and phylogeny. The best model organisms are also small and reproduce quickly. After searching model organism databases, the following model organisms have tubby mutants that can be used to further study this gene and its potential mechanism.
Since the tubby mutation was first identified in mice, they are a common model organism, especially for identifying phenotypes whose mechanisms can then be studied in simpler organisms. Mice carrying the original tubby mutation on varying genetic backgrounds are available from JAX laboratories. Embryonic stem cells have also been developed to allow for conditional knockout of tub. In addition to an obesity phenotype, tubby mice also display altered metabolism, increased food intake, and hearing and vision problems as discussed throughout this site. [1]
Fruit flies, or Drosophila melanogaster, can also be used to study king tubby (the homologue of tubby found in fruit flies). Since fruit flies can be genetically manipulated easily and reproduce quickly, they can often be used to study mechanisms of phenotypes observed in other model organisms, such as mice, much more quickly. Similar to tubby mice, RNAi screens against king tubby and king tubby mutants have altered metabolism of starch, sucrose, and triglycerides (fats), as well as vision problems. Mutants with UAS constructs and enhancer traps are available. A number of other RNAi screens have also been performed and are available for future use.[2,3]
Similar to fruit flies, the flatworm, or C. elegans is often used to study tub-1 (the tubby C. elegans homologue) due to its fast reproduction and ability for hermaphroditic reproduction. The ease of genetic engineering using RNAi also make C. elegans a useful model organism. RNAi knockdown of tub-1 results in increased fat accumulation and increased life span. [4] Two tub-1 deletion models and several reporter gene models (GFP) are also available for future use. [5]
Although plants are not often thought of as a model system for human disease, tubby is so well conserved that an Arabidopsis homologue, tlp3 has been identified. Tlp3 has been shown to be involved in stress signaling, a biological process related to metabolism. Several germplasm stocks containing tlp3 single nucleotide polymorphisms (SNPs) are available for study. [6]
Analysis of Tubby model organisms
While tubby mutants have been identified in all of the above model organisms, the usefulness of each depends on your research question. Drosophila and C. elegans are a good model for performing screens of potential tubby targets both upstream and downstream of tubby itself, as well as beginning to decipher metabolic aspects of the disease. It is interesting, however, that no phenotype in feeding behavior has been identified or recorded in model organisms outside of mice. Determining whether this feeding behavior phenotype is conserved in other model organisms is a future direction for research. Therefore, in order gain a better understanding of how tub affects feeding behavior, mice were used in my specific aims.
References
Cover Photo Credit
[1] The Jackson Laboratory. Tub Mice. Mouse Genome Database.
[2] Flybase. Gene dmel/ktub.
[3] FLIGHT. v. 2.0. King tubby.
[4] WormBase. Tub-1 (gene).
[5] RNAi database. tub-1 RNAi experiments.
[6] TAIR. Locus: AT2G47900.
[1] The Jackson Laboratory. Tub Mice. Mouse Genome Database.
[2] Flybase. Gene dmel/ktub.
[3] FLIGHT. v. 2.0. King tubby.
[4] WormBase. Tub-1 (gene).
[5] RNAi database. tub-1 RNAi experiments.
[6] TAIR. Locus: AT2G47900.
Site created by Rachael Baird.
Genetics 564 Assignment, Spring 2014
University of Wisconsin-Madison
Last Updated: 5-10-14
Genetics 564 Assignment, Spring 2014
University of Wisconsin-Madison
Last Updated: 5-10-14