# Construction of a Zebrafish Model of Cardiac Hypertrophy Caused by ATIC Gene Deletion and Preliminary Exploration of Aerobic Exercise Improvement

## TL;DR

This study creates a zebrafish model with a deleted ATIC gene to mimic heart disease and finds that aerobic exercise can improve heart function and symptoms.

## Contribution

A novel zebrafish model of HCM caused by ATIC deletion and evidence that aerobic exercise can alleviate its symptoms.

## Key findings

- ATIC gene deletion in zebrafish causes hypertrophic cardiomyopathy symptoms like heart enlargement and collagen deposition.
- Aerobic exercise improves cardiac function and reduces pathological features in atic−/− zebrafish.
- Transcriptome analysis links aerobic exercise benefits to pathways like calcium signaling and ECM–receptor interaction.

## 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.