Research Progress on the Construction and Application of a Diabetic Zebrafish Model
Abstract
:1. Introduction
2. Methods of Diabetic Zebrafish Model Construction
2.1. Type I Diabetes Model Construction Methods
2.1.1. Method of Surgical Resection
2.1.2. Drug Induction Method
2.1.3. Induction by Genetic Modification
2.2. Construction Methods for Type II Diabetes
2.2.1. Glucose Solution Immersion Method
2.2.2. High-Fat Food Induction Method
2.2.3. CRISPR/Cas9 Gene Knockout Method
2.2.4. Genetic Ablation Method
2.3. Evaluation Indicators of Diabetic Zebrafish Models
3. Types of Zebrafish Models of Diabetes and Their Complications
3.1. Maturity-Onset Diabetes Mellitus Model
3.2. Gestational Diabetes Mellitus Model
3.3. Diabetic Cardiovascular Disease Model
3.4. Diabetic Retinopathy Model
3.5. Neurological Complications
3.6. Diabetic Nephropathy
3.7. Diabetic Wound Model
3.8. Diabetic Immune Injury Model
4. Conclusions and Prospects
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Category | Animal | Advantage | Disadvantage | References |
---|---|---|---|---|
Non-mammalian animals | Zebrafish | As an emerging model, it has the advantages of fast reproduction, copulatory behavior controlled by photoperiod, large number of eggs laid, in vitro fertilization of fertilized eggs, overall transparency of early embryos, easy feeding, and easy use of drugs. | It is an ectothermic animal and lacks brown adipose tissue, so it is still difficult to measure insulin levels and assess insulin resistance. | [15,16,21] |
Drosophila melanogaster | Drosophila is easy to obtain and operate, and has strong conservation with the lipid-related metabolism genes of mammals, which can be used to study the function of candidate genes related to T2DM. | It is distantly related to humans, and its anatomical structure and physiological function are slightly similar to those of the human body. | [22,23] | |
Rodent | Rat and mouse | It is highly productive, low-cost, and diverse, covering obesity and diabetes, with advanced tools for genetic modification and metabolic phenotype assessment. | The structure of islets, basal metabolic rate, feeding behavior, immune system, and gut microbiota are less similar to those of humans. | [24,25,26] |
Large mammals | Pig | The feeding cost is low and wide application is possible. The gene modification technology is relatively mature, and a variety of disease models can be generated through targeted gene editing. | It does not usually lead to diabetes and requires a combination of other means. It also requires special equipment and costs more than small animals. | [13,27,28] |
Non-human primates | Monkey | The anatomical structure, physiological characteristics, and genetic background are similar to those of humans, and the results of the study are of high clinical relevance. | The number of animals is small, the production cycle is long, the fecundity is weak, the technology is imperfect, and the price is high. | [29] |
Type | Construction Method | Advantages | Disadvantages | References |
---|---|---|---|---|
Type I Diabetes | Surgical resection method | The earliest method for replication of animal models of diabetes. | It requires highly skilled operating techniques and elaborate equipment for researchers, and the trauma to zebrafish is significant, resulting in a low survival rate of zebrafish after surgery. | [109,110] |
Drug induction method | With the advantages of short time frames, simplicity, ease of mastery, and good repeatability, a large number of models can be induced in a short period of time. | Multiple intraperitoneal injections of streptozotocin are needed, and the operation is complicated. | [111,112,113] | |
Induction by genetic modification | Transgenic technology can be used to construct zebrafish with specific functions. | Transgenes will damage other genes in the genome, resulting in the loss of other functional genes, and the acquisition of homozygotes takes a long time. | [108,114] | |
Genetic ablation method | Target cell populations in zebrafish larvae can be effectively removed by the NTR/MTZ system. | This approach has limitations due to the instability and uncertainty of current techniques regarding the genetic aspects. | [108,109,115] | |
Type II Diabetes | Glucose solution immersion method | The feeding procedure is simple and the diabetic model can be established in about ten days. | In solutions with high concentrations of sugar, the swimming and gill functions of the zebrafish were abnormal, and some zebrafish died in the modeling process. | [116] |
High-fat food induction method | The feeding procedure is simple. | It takes a long time, and obesity often leads to cardiovascular disease and endocrine abnormalities. | [90] | |
CRISPR/Cas9 gene knockout method | Knockout zebrafish can be obtained quickly. | In the face of gene editing, the target gene is off-target, and there is genetic instability after editing. | [117] |
Type of Diabetic Zebrafish Model | Construction Method | Phenotypic Characteristics | References |
---|---|---|---|
Juvenile diabetes model | Mutation of hepatic nuclear factor 1β(HNF-1β) gene | Early onset, autosomal dominant inheritance, diabetes mellitus, renal cysts (dysplastic glomerular cystic lesions), and even nondiabetic renal insufficiency. | [149,150] |
Gestational diabetes model | Glucose immersion method | The total free glucose level of zebrafish embryos in high glucose group fluctuated in a dose-dependent manner, and the average free glucose level increased significantly. | [151] |
Diabetic cardiovascular disease model | Glucose immersion method | Zebrafish treated with high glucose concentrations gradually showed cardiac hypertrophy, apoptosis, and arrhythmia. Early diastolic dysfunction and late systolic dysfunction occurred in the heart. | [113] |
Diabetic retinopathy model | Glucose immersion method | The internal layer and core layer of zebrafish in the diabetes model group were significantly lower than those in the normal group, and the IPL was significantly thinner. | [100,109] |
Neurological complications | Glucose immersion method | Hyperglycemia can regulate acetylcholinesterase function and gene expression in zebrafish, leading to choline dysfunction and eventual memory loss. | [121,123,137] |
Renal complications | CRISPR/Cas9 gene knockout (CRISPR/Cas9-induced ELMO1 deletion in 48hpf embryos) | The basal glomerular membrane was thickened. | [128,138] |
Diabetic wound model | Streptozotocin drug induction method | In diabetic zebrafish, fin regeneration and skin wound healing are impaired and persist even after blood sugar levels return to normal. | [152,153] |
Diabetic immune damage model | The dominant negative mutant of insulin-like growth factor 1 receptor was constructed by using the dominant negative effect. | In this model, ER stress led to an increase in the number of macrophages and neutrophils, and neutrophils attacked beta cells in contact with the macrophages, causing them to be lost. | [91] |
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Cao, Y.; Chen, Q.; Liu, Y.; Jin, L.; Peng, R. Research Progress on the Construction and Application of a Diabetic Zebrafish Model. Int. J. Mol. Sci. 2023, 24, 5195. https://doi.org/10.3390/ijms24065195
Cao Y, Chen Q, Liu Y, Jin L, Peng R. Research Progress on the Construction and Application of a Diabetic Zebrafish Model. International Journal of Molecular Sciences. 2023; 24(6):5195. https://doi.org/10.3390/ijms24065195
Chicago/Turabian StyleCao, Yu, Qianqian Chen, Yinai Liu, Libo Jin, and Renyi Peng. 2023. "Research Progress on the Construction and Application of a Diabetic Zebrafish Model" International Journal of Molecular Sciences 24, no. 6: 5195. https://doi.org/10.3390/ijms24065195