This web page was produced as an assignment for Genetics 564, an undergraduate capstone course at UW-Madison.
How are model organisms used to study genes?
Model organisms are species who have biological processes that are of interest to researchers. In the case of a AIRE, model organisms are those which express a homolog of AIRE and can be used in to learn about AIRE's function. AIRE is conserved in many species, including chimpanzees, zebrafish, dogs, rats, zebrafish, and mice [1]. However, the main model organism used to study AIRE is the mouse because mice have immune systems to humans and AIRE knockout mice exhibit biological similarities to APECED patients. Furthermore, mice are commonly used in research because they quickly reproduce, like other model organisms including flies or zebrafish, but they also develop diseases similar to those in humans or other mammals [2]. Model organisms studies often knockout a gene of interest by causing a mutation in the gene that interrupts its function or by removing the gene from the organism entirely. Knockout studies provide useful information about the function of a gene because we can study what changes when the gene of interest is gone.
What model organisms can be used to study AIRE?
Mice that are knockouts for AIRE, meaning they are AIRE-/-, have autoimmune symptoms that are similar to APECED patients [3]. AIRE knockout mice have increased autoantibody levels, increased T cell number, abnormal thymus medulla morphology, and inflammation [4]. AIRE deficient mice, unlike humans with APECED, were able to control a Candida infection which suggests that there are still genetic or environmental differences between AIRE deficiency in mice and humans [5]. Mice are used as model organisms for AIRE deficiency because they exhibit similar phenotypic effects to AIRE deficient humans along with the fact that they quickly replicate.
Zebrafish are commonly used as model organisms for human disorders [6]. However, while AIRE mutations can be made in zebrafish, there is no phenotypic data about the effects of AIRE mutations in zebrafish [7].
References
[1] https://www.ncbi.nlm.nih.gov/gene/326
[2] National Human Genome Research Institute. Background on mouse as a model organism. https://www.genome.gov/10005834/background-on-mouse-as-a-model-organism/
[3] Ramsey et al. 2002. Aire deficient mice develop multiple features of APECED phenotype and show altered immune response. https://www.ncbi.nlm.nih.gov/pubmed/11854172
[4] AIRE phenotype annotations related to immune system. http://www.informatics.jax.org/diseasePortal/popup?isPhenotype=true&markerID=MGI:1338803&header=immune%20system
[5] Hubert et al. 2009. Aire-deficient C57BL/6 mice mimicking the common human 13-base pair deletion mutation present with only a mild autoimmune phenotype. http://www.ncbi.nlm.nih.gov/pubmed/19265170
[6] Dooly and Zon. 2000. Zebrafish: a model system for the study of human disease. https://www.ncbi.nlm.nih.gov/pubmed/10826982
[7] ZFIN. Autoimmune regulator. http://zfin.org/ZDB-GENE-071008-4
[1] https://www.ncbi.nlm.nih.gov/gene/326
[2] National Human Genome Research Institute. Background on mouse as a model organism. https://www.genome.gov/10005834/background-on-mouse-as-a-model-organism/
[3] Ramsey et al. 2002. Aire deficient mice develop multiple features of APECED phenotype and show altered immune response. https://www.ncbi.nlm.nih.gov/pubmed/11854172
[4] AIRE phenotype annotations related to immune system. http://www.informatics.jax.org/diseasePortal/popup?isPhenotype=true&markerID=MGI:1338803&header=immune%20system
[5] Hubert et al. 2009. Aire-deficient C57BL/6 mice mimicking the common human 13-base pair deletion mutation present with only a mild autoimmune phenotype. http://www.ncbi.nlm.nih.gov/pubmed/19265170
[6] Dooly and Zon. 2000. Zebrafish: a model system for the study of human disease. https://www.ncbi.nlm.nih.gov/pubmed/10826982
[7] ZFIN. Autoimmune regulator. http://zfin.org/ZDB-GENE-071008-4
Image References
[1] https://www.pinterest.com/skippybme/
[2] http://www.noldus.com/animal-behavior-research/solutions/zebrafish
[1] https://www.pinterest.com/skippybme/
[2] http://www.noldus.com/animal-behavior-research/solutions/zebrafish