PUBLICATION
lmod2a Mutations Affect F-actin and SRF Pathway Leading to Cardiac Dysfunction in Zebrafish
- Authors
- Ye, X., Jia, H., Zu, Y.
- ID
- ZDB-PUB-250610-13
- Date
- 2025
- Source
- Developmental Biology : (Journal)
- Registered Authors
- Keywords
- CRISPR/Cas9, DCM, F-actin, SRF, lmod2a
- MeSH Terms
-
- Muscle Proteins*/genetics
- Muscle Proteins*/metabolism
- Cardiomyopathy, Dilated/genetics
- Animals
- CRISPR-Cas Systems
- Zebrafish Proteins*/genetics
- Zebrafish Proteins*/metabolism
- Signal Transduction/genetics
- Microfilament Proteins*/genetics
- Microfilament Proteins*/metabolism
- Heart*/embryology
- Heart*/physiopathology
- Disease Models, Animal
- Serum Response Factor*/genetics
- Serum Response Factor*/metabolism
- Actins*/genetics
- Actins*/metabolism
- Mutation/genetics
- Zebrafish*/embryology
- Zebrafish*/genetics
- Zebrafish*/metabolism
- PubMed
- 40490045 Full text @ Dev. Biol.
Citation
Ye, X., Jia, H., Zu, Y. (2025) lmod2a Mutations Affect F-actin and SRF Pathway Leading to Cardiac Dysfunction in Zebrafish. Developmental Biology. :.
Abstract
Leiomodin 2 (LMOD2), a critical pathogenic gene associated with human dilated cardiomyopathy (DCM), is essential in regulating thin filament length during cardiac development. This study generated a homozygous knockout zebrafish line (lmod2a-/-) using CRISPR/Cas9 genome editing. lmod2a-/- embryos exhibited impaired locomotor activity alongside irregular heart rhythms, reduced cardiac output, compromised contractility, and delayed calcium transients, as revealed by high-speed imaging and calcium optical mapping. Immunofluorescence staining demonstrated a marked reduction in filamentous actin (F-actin), corroborated by QPCR data showing downregulation of the F-actin marker gene acta1b. Moreover, expression levels of key downstream targets of the serum response factor (SRF) signaling pathway were markedly reduced in mutants. These findings indicate that lmod2a deficiency disrupts F-actin homeostasis and SRF-mediated gene regulation, ultimately leading to defective cardiac performance. This study establishes a novel zebrafish model for investigating LMOD-associated cardiomyopathies and provides valuable insights for future therapeutic interventions targeting actin-related cardiac disorders.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping