What are Model Organisms?
A Model Organism is a widely studied species selected for its experimental advantages. They are usually easy to maintain and breed in a laboratory setting, and provide vast insight into biological processes which cannot be tested in Humans [2,3]. Many mutant model organisms have been created with the use of CRISPR gene editing or with specific RNAi knockdown properties which allow phenotypes to be observed that correspond to the mutated or knocked-out gene of interest.
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What is the Mutant GFAP Phenotype in Mice and Zebrafish?
Mouse:
Homozygotes for GFAP knockouts in mice showed reduced astrocyte-associated intermediate filaments, enhanced long term potentiation, and impaired eye-blink conditioning. Aged mice sometimes showed hydrocephaly, reduced myelination, and an impaired blood-brain barrier [1]. Transgenic Human GFAP in mice also caused the aggregation of GFAP, forming Rosenthal Fibers [1]. |
Zebrafish:
No phenotypes have been recorded for mutations of the GFAP homolog in Zebrafish on ZFIN. Transgenic expression of AD causing mutated Human GFAP in Zebrafish resulted in an accumulation of GFAP aggregates similiar to Rosenthal fibers [4]. |
Discussion
Due to the significant role mutated GFAP has in AD in humans, it would be expected that these same mutations in model organisms would cause similar phenotypes, though for current research this seems to not be the case. This could indicate that these organisms are more capable at handling the toxicity caused by gain of function mutations to their GFAP homologs, because rosenthal fibers are only observed when human transgenic GFAP is inserted into mouse and zebrafish models.
References
[1] Gfap MGI Mouse Gene Detail - MGI:95697 - glial fibrillary acidic protein. (n.d.). Retrieved March 15, 2018, from http://www.informatics.jax.org/marker/MGI:95697
[2] Skop, A. (2018). Lab 4: Model Organisms. Retrieved March 15, 2018, from http://genetics564.weebly.com/rnai-databases.html
[3] What are model organisms? (n.d.). Retrieved March 15, 2018, from /facts/what-are-model-organisms
[4] ZFIN Gene: gfap. (n.d.). Retrieved March 15, 2018, from http://zfin.org/ZDB-GENE-990914-3
[2] Skop, A. (2018). Lab 4: Model Organisms. Retrieved March 15, 2018, from http://genetics564.weebly.com/rnai-databases.html
[3] What are model organisms? (n.d.). Retrieved March 15, 2018, from /facts/what-are-model-organisms
[4] ZFIN Gene: gfap. (n.d.). Retrieved March 15, 2018, from http://zfin.org/ZDB-GENE-990914-3