This web page was produced as an assignment for Genetics 564, an undergraduate capstone course at UW-Madison.
What are model organisms?
Model organisms are a specific subset of research organisms that serve as a proxy for understanding biological processes [1]. These organisms are usually easy to maintain and breed. They often have shorter generation times, and are quicker to maturation, making them useful for research of human diseases or processes.
What are common model organisms?[2]
Saccharomyces cerevisiae (Baker's Yeast)
Baker's yeast are convenient for study because they grow quickly and are cheap to maintain. The entire genome has been sequenced and annotated. Additionally, yeast are eukaryotic (have a nucleus) but are single celled. Yeast are commonly used to study biological processes.
Baker's yeast are convenient for study because they grow quickly and are cheap to maintain. The entire genome has been sequenced and annotated. Additionally, yeast are eukaryotic (have a nucleus) but are single celled. Yeast are commonly used to study biological processes.
Caenorhabditis elegans (Roundworm)
This nematode was the first multicellular organism to have its entire genome sequenced. They are small, cheap, and have a short generation time. They are commonly used to study development, cell cycles, aging, and simple nervous systems.
This nematode was the first multicellular organism to have its entire genome sequenced. They are small, cheap, and have a short generation time. They are commonly used to study development, cell cycles, aging, and simple nervous systems.
Danio rerio (Zebrafish)
Zebrafish are small and relatively cheap to maintain and breed. They have transparent embryos which make zebrafish useful for studying development. They are commonly used for mapping and identifying genes involved in organ development. They have a fully sequenced genome, which makes them useful for genetic engineering.
Zebrafish are small and relatively cheap to maintain and breed. They have transparent embryos which make zebrafish useful for studying development. They are commonly used for mapping and identifying genes involved in organ development. They have a fully sequenced genome, which makes them useful for genetic engineering.
Drosophila melanograster (Fruitfly)
Fruitflies are multicellular organisms. They have a very fast maturation rate and a short lifespan making them useful for research studies. They are also cheap to maintain and breed. Fruitfly has very large chromosomes which have been used in studies to observe linkage and recombination. They have also been used to study early development and complex biological functions.
Fruitflies are multicellular organisms. They have a very fast maturation rate and a short lifespan making them useful for research studies. They are also cheap to maintain and breed. Fruitfly has very large chromosomes which have been used in studies to observe linkage and recombination. They have also been used to study early development and complex biological functions.
Mus musculus (House mouse)
The mouse is a mammal which has very similar anatomic structure to humans, making them an especially useful model organism for studying human diseases. They have significantly shorter lifespan and maturation rate than humans, so they are more convenient for human disease studies. The mouse genome has also been fully sequenced and many mutations in mice have similar phenotypes to humans.
The mouse is a mammal which has very similar anatomic structure to humans, making them an especially useful model organism for studying human diseases. They have significantly shorter lifespan and maturation rate than humans, so they are more convenient for human disease studies. The mouse genome has also been fully sequenced and many mutations in mice have similar phenotypes to humans.
What model organisms should be used for studying CLD?
The three closest relatives to humans, based on the LCT protein homolog phylogenetic trees, are mouse, rat, and zebrafish.
A zebrafish strain has been reported with a point mutation that results in a premature stop codon during translation[3]. While this is a similar mutation to the human CLD mutations, zebrafish would be difficult to study to phenotype of diarrhea, and the duplication of the protein domains in the zebrafish homolog makes it not the most ideal organism for studying CLD. Zebrafish also preferentially use lipids, rather than carbohydrates, as an energy source, which differs from mammals[6].
The rat and mouse are most similar to humans because they are both mammals with similar anatomy. There are no reported rat strains with an LCT mutation[4]. There are four mice strains with LCT mutations[5]. However all of these mutations are knockout mutations, which would not help elucidate how single amino acid changes at the C-terminus glycosyl hydrolase domain cause CLD. Although there are no existing mutant mice lines, mice are still the model organism of choice for this study. The homolog is very similar, with matching domains to the human domain. Additionally the gene maintains the same functions in mice as it does in humans. Mice also evolved similar to humans, in that young mice actually consume lactose from their mother's milk. Finally, the disease phenotype of diarrhea will be easily assayed in mice, making it convenient for studying CLD.
A zebrafish strain has been reported with a point mutation that results in a premature stop codon during translation[3]. While this is a similar mutation to the human CLD mutations, zebrafish would be difficult to study to phenotype of diarrhea, and the duplication of the protein domains in the zebrafish homolog makes it not the most ideal organism for studying CLD. Zebrafish also preferentially use lipids, rather than carbohydrates, as an energy source, which differs from mammals[6].
The rat and mouse are most similar to humans because they are both mammals with similar anatomy. There are no reported rat strains with an LCT mutation[4]. There are four mice strains with LCT mutations[5]. However all of these mutations are knockout mutations, which would not help elucidate how single amino acid changes at the C-terminus glycosyl hydrolase domain cause CLD. Although there are no existing mutant mice lines, mice are still the model organism of choice for this study. The homolog is very similar, with matching domains to the human domain. Additionally the gene maintains the same functions in mice as it does in humans. Mice also evolved similar to humans, in that young mice actually consume lactose from their mother's milk. Finally, the disease phenotype of diarrhea will be easily assayed in mice, making it convenient for studying CLD.
Conclusions
Model organisms are very useful for studying human diseases due to their shorter generation times, and ease of maintenance and breeding. Since mice have similar anatomy, a close homolog of LCT, and similar protein function of lactase, they are the organism of choice for this study. Additionally, diarrhea, which is the disease phenotype in humans, will be easy to observe in mice. A new strain will be created with an induced point mutation, resulting in a single amino acid substitution in the C-terminus glycosyl hydrolase family 1 domain of LCT.
References
[1] National Institute of General Medical Sciences. (2017, October). Using Research Organisms to Study Health and Disease. www.nigms.nih.gov/Education/Pages/modelorg_factsheet.aspx
[2] Simmons, D. (2008). The Use of Animal Models in Studying Genetic Disease: Transgenesis and Induced Mutation. Nature Education. Retrieved from www.nature.com/scitable/topicpage/the-use-of-animal-models-in-studying-855
[3] Zebrafish Information Network (ZFIN). University of Orgeon, Eugene. zfin.org/ZDB-GENE-081104-434
[4] The Rat Genome Database (RGD). Medical College of Wisconsin, Milwaukee WI. rgd.mcw.edu/rgdweb/report/gene/main.html?id=620823
[5] The International Mouse Strain Resource (IMSR). www.findmice.org/summary?gaccid=MGI:104576
[6] Santoro, M. (2014, October). Zebrafish as a model to explore cell metabolism. Trends in Endocrinology and Metabolism. Retrieved from www.cell.com/trends/endocrinology-metabolism/fulltext/S1043-2760(14)00102-7
Header Image: www.yourgenome.org/facts/what-are-model-organisms