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21世紀におけるゼブラフィッシュ創薬のグローバル展開

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2024/09/10
Zebrafish-Based Oncocardionephrology

》Zebrafish and Mouse Gene KO Kidney Disease Models in Drug Discovery Research

                     
2023/07/24

Zebrafish and mouse gene KO kidney disease models are two commonly used models in drug discovery research.
Here are some advantages and disadvantages of each model:

ZebrafishGene KO Kidney Disease Model
The zebrafish model is a versatile small vertebrate organism that is widely used for studying human inherited diseases 2
Some advantages of using zebrafish as a model for drug screening in genetic kidney diseases include:

1)Cost-effective whole-organism chemical screening 2

2)Identification of novel drug targets 2

3)High-throughput and high-content phenotypic drug screening 6

4)Clinically relevant and highly conserved disease characteristics, aetiology, and progression 6

However, there are also some disadvantages to using zebrafish as a model:
1)Lack of an established protocol, which limits the ability to make meaningful comparisons and draw significant conclusions among different studies 8
2)Limited understanding of the crosstalk among cells and the subsequent complex in vivo responses in chronic kidney disease (CKD) 15
3)Zebrafish’s low genetic similarity to humans 15

Mouse Gene KO Kidney Disease Model
Mouse gene KO kidney disease models are used to model congenital human disease in animals, which is key to our understanding of the biological mechanism underlying pathological processes and thus developing novel potential treatment options 1
Some advantages of using mouse gene KO kidney disease models include:
1)Robust functional readouts, such as proteinuria, GFR, and secondary hypertension 1
2) Reliable induction in rodents 1
3)The ability to tag and select specific kidney cell types or disease-specific gene knock in/out, which enables more precise and targeted drug discovery 1

However, there are also some disadvantages to using mouse gene KO kidney disease models:
1)These models do not exactly simulate human diseases, and most of them are strain, gender, or age dependent 1
2)Results are limited and can mainly be interpreted as individual and specific responses unique to only the cell type studied 1

In conclusion, both zebrafish and mouse gene KO kidney disease models have advantages and disadvantages in drug discovery research.
Researchers should choose the most appropriate model based on their research questions and goals.

References:
1.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3030258/
2.https://www.frontiersin.org/articles/10.3389/fped.2018.00183/full
3.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5885387/
4.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7162671/
5.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7299748/
6.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9210578/
7.https://link.springer.com/protocol/10.1007/978-1-0716-0978-1_2
8.https://portlandpress.com/bioscirep/article/37/3/BSR20170199/57106/Zebrafish-models-for-functional-and-toxicological
9.https://academic.oup.com/ndt/article/28/10/2432/1806279
10.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6031734/
11.https://www.future-science.com/doi/10.2144/fsoa-2021-0019
12.https://anatomypubs.onlinelibrary.wiley.com/doi/full/10.1002/dvdy.21967
13.https://bmcnephrol.biomedcentral.com/articles/10.1186/1471-2369-14-116
14.https://www.nature.com/articles/nrd1606
15.https://www.sciencedirect.com/science/article/pii/S2405844023017644
16.https://lupus.bmj.com/content/5/1/e000199
17https://www.sciencedirect.com/science/article/pii/S0085253816003811

関連リンク

三重大学大学院医学系研究科システムズ薬理学

三重大学メディカルゼブラフィッシュ研究センター