PUBLICATION
Construction of a Zebrafish Model of Cardiac Hypertrophy Caused by ATIC Gene Deletion and Preliminary Exploration of Aerobic Exercise Improvement
- Authors
- Yang, T., Zhang, Z., Huang, S., Cui, M., Liu, S., Ding, M., Gu, W., Yang, B., Zheng, L.
- ID
- ZDB-PUB-251113-15
- Date
- 2025
- Source
- International Journal of Molecular Sciences 26: (Journal)
- Registered Authors
- Keywords
- ATIC, CRISPR/Cas9, aerobic exercise intervention, hypertrophic cardiomyopathy, transcriptome analysis, zebrafish
- MeSH Terms
-
- Animals
- Cardiomegaly*/genetics
- Cardiomegaly*/metabolism
- Cardiomegaly*/pathology
- Cardiomegaly*/therapy
- Cardiomyopathy, Hypertrophic*/genetics
- Disease Models, Animal
- Gene Deletion*
- Physical Conditioning, Animal*
- Zebrafish/genetics
- Zebrafish Proteins*/genetics
- PubMed
- 41226290 Full text @ Int. J. Mol. Sci.
Citation
Yang, T., Zhang, Z., Huang, S., Cui, M., Liu, S., Ding, M., Gu, W., Yang, B., Zheng, L. (2025) Construction of a Zebrafish Model of Cardiac Hypertrophy Caused by ATIC Gene Deletion and Preliminary Exploration of Aerobic Exercise Improvement. International Journal of Molecular Sciences. 26:.
Abstract
Hypertrophic cardiomyopathy (HCM) is a relatively common global cardiac disease, usually inherited, with complex phenotypes, genetic features, and a natural history. In this study, we constructed atic-/- zebrafish using the CRISPR/Cas9 gene-editing system and found that atic-/- zebrafish hearts exhibited HCM symptoms, and atic-/- zebrafish hearts showed progressive enlargement, eccentric hypertrophy, cardiomyocyte enlargement, and collagen fiber deposition. Echocardiography results also showed that compared with atic-/- zebrafish hearts, in wild-type zebrafish hearts, the ejection fraction was significantly reduced, shortening fraction was reduced, and ventricular wall thickness was significantly increased. Meanwhile, aerobic exercise intervention in atic-/- zebrafish showed that aerobic exercise effectively improved the symptoms of HCM and improved cardiac function in atic-/- zebrafish hearts. Transcriptome sequencing results showed that aerobic exercise improved the symptoms of HCM in atic-/- zebrafish hearts involving the calcium signaling pathway, Apelin signaling pathway and ECM-receptor interaction. The q-PCR results of key differential genes involved in these pathways further confirmed that aerobic exercise could bring beneficial effects to atic-/- zebrafish. In conclusion, this study found that the loss of ATIC can lead to hypertrophic cardiomyopathy in zebrafish, and aerobic exercise intervention can effectively improve the hypertrophic pathological characteristics of atic-/- zebrafish hearts, providing new intervention targets and effective lifestyle interventions for HCM.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping