Model organisms are groups of non-human species that have been studied extensively to conduct further research on human biological processes, diseases, & targeted drug therapy. These species are relatively manageable to maintain and breed in a laboratory setting[1]. Selection for the best organism model depends on the specific research conducted such as: studying the immune system, neural networks, & the central nervous system.
Model Animals Compatible to Study ADA1
Mice: Humans share on average 85% of identical protein coding DNA with mice [1]. The mice genome is also almost identical in size as the human genome with and was the second mammalian genome fully sequenced after human [2]. Many regulatory regions of the mouse and human genome are heavily conserved among both species making them a suitable model organism for studying different tissues such as the heart, brain, blood & circulatory system [3].
Zebrafish: Danio rerio share on average 70% of their genome with humans. Upon genetic identity it appears that mice would be the better model organism due to their closer similarities. However, zebrafish have several advantages over mice. Since adult zebrafish are small, they more can be house in the same tank vs mice and also require cheaper maintenance [4]. Embryos are also laid outside the mother fish which enables scientist to perform in-vitro fertilization and be able to modify the zebrafish genome with much less complications. Observations of live development are also possible in zebrafish embryos as they are naturally clear colored. This phenotype allows for fluorescently labeled tissues in transgenic zebrafish lines [4].While studies have been conducted on Zebrafish to study SCID by analysing ectopic expression of targeted knockouts, no studies particularly focus on the role of ADA1.
Targeting of Mice/ Experimental Construct
Mice was selected as the organism model of choice due to their closer physiological similarities with humans thn Zebrafish. They have also taken a greater role in modeling immune system disease as they show higher matching homolgy among protein sequences involved in molecular pathways with metabolism that can lead to a more precise study of the way particular domains such as the cAMP protein kinase inhbitor gamma is involved in altering the purine metabolism pathway leading to pulmonary abnormalies found post-therapy [6]. |
References
[1] Immune Deficiency Foundation: The Story of David. <https://primaryimmune.org/living-pi-explaining-pi-others/story-david>
[2]Whitte H, Thrasher A, Veys P, Kinnon C, Gaspar HB. Intrinsic defects of B cell function in X-linked severe combined immunodeficiency. Eur J Immunol. 2000;30:772–7.
[3] Adenosine Deaminase Deficiency More than just an Immunodeficicency https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4985714/pdf/fimmu-07-00314.pdf
[4] Drug Information Portal https://druginfo.nlm.nih.gov/drugportal/name/adagen \March 2018
[5] Komarow HD, Sokolic R, Hershfield MS, Kohn DB, Young M, Metcalfe DD, et al. Impulse oscillometry identifies peripheral airway dysfunction in children with adenosine deaminase deficiency. Orphanet J Rare Dis (2015)
[6] Adenosine Deaminase Deficiency More than just an Immunodeficicency https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4985714/pdf/fimmu-07-00314.pdf
[1] Immune Deficiency Foundation: The Story of David. <https://primaryimmune.org/living-pi-explaining-pi-others/story-david>
[2]Whitte H, Thrasher A, Veys P, Kinnon C, Gaspar HB. Intrinsic defects of B cell function in X-linked severe combined immunodeficiency. Eur J Immunol. 2000;30:772–7.
[3] Adenosine Deaminase Deficiency More than just an Immunodeficicency https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4985714/pdf/fimmu-07-00314.pdf
[4] Drug Information Portal https://druginfo.nlm.nih.gov/drugportal/name/adagen \March 2018
[5] Komarow HD, Sokolic R, Hershfield MS, Kohn DB, Young M, Metcalfe DD, et al. Impulse oscillometry identifies peripheral airway dysfunction in children with adenosine deaminase deficiency. Orphanet J Rare Dis (2015)
[6] Adenosine Deaminase Deficiency More than just an Immunodeficicency https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4985714/pdf/fimmu-07-00314.pdf