This web page was produced as an assignment for Genetics 564, an undergraduate course at UW-Madison.
Model Organism Databases
Model organism databases are used to identify mutant phenotypes that have been previously studied. To study disease models, it is fundamental to first understand the mutant phenotypes in the model organisms. Because of the complexity of the human body and the ethical issues in regards to human research studies, it is incredibly difficult to study disease in humans. Therefore, model organisms provide a simpler and more efficient way to study disease and potential treatments. Below are some common model organisms (including the mutant phenotypes found in regards to the SEMA5A gene) that are typically used in research and mentioned throughout this website.
SEMA5A Mutant Phenotypes in Model Organisms
Drosophila melanogaster (Fruitfly)
There are no mutant lines of Sema5a publicly available, according to Flybase. However, there are mutants lines of other Sema genes (such as: Sema1a, Sema1b, Sema2a, Sema5c) that are available publicly.
Mus musculus (Mouse)
There are several knockouts of Sema5a publicly available, some of which reported mutant phenotypes. In a targeted null/knockout, complete embryonic lethality during organogenesis was observed. This knockout also had abnormal blood vessel morphology, specifically seen in the branching of the cranial blood vessels [1].
Rattus norvegicus (Rat)
There are several Sema5a strain sequence variants publicly available, although no mutant phenotypes were reported [2].
Danio rerio (Zebrafish)
There are three knockouts of sema5a publicly available, some of which reported mutant phenotypes. The mutant phenotypes observed include: delayed axon extension, disrupted motor neuron length, and abnormal motor neuron hypoplasticity [3].
What is RNA Interference (RNAi)?
RNA interference, or RNAi, is used to knockdown the function of a gene by utilizing manufactured double-stranded RNA. Mutant phenotypes that are characteristically seen in human diseases can be obtained by incomplete knockdown. This can be useful in syndromes or diseases similar to Cri du Chat, where the severity of the syndrome/disease is dependent on the deletion size. The size of the gene mutation can easily be manipulated using RNAi, making the mutant model organisms more representative of the syndrome or disease being studied.
Although this technology would be ideal for studying Sema5a mutations, there currently are not any RNAi systems for Sema5a available to the public.
Although this technology would be ideal for studying Sema5a mutations, there currently are not any RNAi systems for Sema5a available to the public.
Video 1. Youtube 3.29.2008. RNA Interference (RNAi). Retrieved from here.
Discussion
Because Sema5A is involved in neuronal development and vasculature patterning, it is expected that the deletion of this gene in models would result in abnormal blood vessel morphology, delayed axon extension, disrupted motor neuron length, and abnormal motor neuron hypoplasticity. Since neuronal development and vasculature patterning are necessary for organismal survival, it is expected that the phenotypes observed are severe, such as embryonic lethal in some cases.
Although there are limited resources in regards to the Sema5a gene in model organisms, the phenotypes observed in the mouse and zebrafish knockouts are consistent with those seen in Cri du Chat patients. The zebrafish is an efficient and cost-effective model organism, making it an ideal candidate for the screening of Sema5a mutants.
The development of RNAi technology in Sema5a could potentially lead to an incomplete knockdown of the target gene, which could be used as a more variant representation of Cri du Chat patients and the array of symptoms observed.
Although there are limited resources in regards to the Sema5a gene in model organisms, the phenotypes observed in the mouse and zebrafish knockouts are consistent with those seen in Cri du Chat patients. The zebrafish is an efficient and cost-effective model organism, making it an ideal candidate for the screening of Sema5a mutants.
The development of RNAi technology in Sema5a could potentially lead to an incomplete knockdown of the target gene, which could be used as a more variant representation of Cri du Chat patients and the array of symptoms observed.
References
Youtube video: https://youtu.be/gZZyxVP02UU
[1] Sema5a Targeted Allele Detail MGI Mouse (MGI:3577050). (n.d.). Retrieved March 24, 2015, from http://www.informatics.jax.org/allele/MGI:3577050
[2] Sema5a (sema domain, seven thrombospondin repeats (type 1 and type 1-like), transmembrane domain (TM) and short cytoplasmic domain, (semaphorin) 5A) - Rat Genome Database. (n.d.). Retrieved March 24, 2015, from http://www.rgd.mcw.edu/rgdweb/report/gene/main.html?id=1308650
[3] ZFIN Morpholino: MO1-sema5a. (n.d.). Retrieved March 24, 2015, from http://zfin.org/action/marker/view/ZDB-MRPHLNO-090811-1
[1] Sema5a Targeted Allele Detail MGI Mouse (MGI:3577050). (n.d.). Retrieved March 24, 2015, from http://www.informatics.jax.org/allele/MGI:3577050
[2] Sema5a (sema domain, seven thrombospondin repeats (type 1 and type 1-like), transmembrane domain (TM) and short cytoplasmic domain, (semaphorin) 5A) - Rat Genome Database. (n.d.). Retrieved March 24, 2015, from http://www.rgd.mcw.edu/rgdweb/report/gene/main.html?id=1308650
[3] ZFIN Morpholino: MO1-sema5a. (n.d.). Retrieved March 24, 2015, from http://zfin.org/action/marker/view/ZDB-MRPHLNO-090811-1