PUBLICATION
A CRISPR/Cas9 zebrafish lamin A/C mutant model of muscular laminopathy
- Authors
- Nicolas, H.A., Hua, K., Quigley, H., Ivare, J., Tesson, F., Akimenko, M.A.
- ID
- ZDB-PUB-211003-3
- Date
- 2022
- Source
- Developmental Dynamics : an official publication of the American Association of Anatomists 251(4): 645-661 (Journal)
- Registered Authors
- Akimenko, Marie-Andree
- Keywords
- Emery-Dreifuss muscular dystrophy (EDMD), Protein Kinase C alpha (PKC α), striated muscle laminopathies
- MeSH Terms
-
- Animals
- CRISPR-Cas Systems
- Disease Models, Animal
- Lamin Type A*/genetics
- Lamin Type A*/metabolism
- Laminopathies*
- Muscle, Skeletal
- Mutation
- Zebrafish/genetics
- Zebrafish/metabolism
- PubMed
- 34599606 Full text @ Dev. Dyn.
Citation
Nicolas, H.A., Hua, K., Quigley, H., Ivare, J., Tesson, F., Akimenko, M.A. (2022) A CRISPR/Cas9 zebrafish lamin A/C mutant model of muscular laminopathy. Developmental Dynamics : an official publication of the American Association of Anatomists. 251(4):645-661.
Abstract
Background Lamin A/C gene (LMNA) mutations frequently cause cardiac and/or skeletal muscle diseases called striated muscle laminopathies. We created a zebrafish muscular laminopathy model using CRISPR/Cas9 technology to target the zebrafish lmna gene.
Results Heterozygous and homozygous lmna mutants present skeletal muscle damage at 1 day post fertilization (dpf), and mobility impairment at 4-7 dpf. Cardiac structure and function analyses between 1-7 dpf show mild and transient defects in the lmna mutants compared to wild type (WT). Quantitative RT-PCR analysis of genes implicated in striated muscle laminopathies show a decrease in jun and nfκb2 expression in 7 dpf homozygous lmna mutants compared to WT. Homozygous lmna mutants have a 1.26-fold protein increase in activated Erk 1/2, kinases associated with striated muscle laminopathies, compared to WT at 7 dpf. Activated Protein Kinase C alpha (Pkc α), a kinase that interacts with lamin A/C and Erk 1/2, is also upregulated in 7 dpf homozygous lmna mutants compared to WT.
Conclusions This study presents an animal model of skeletal muscle laminopathy where heterozygous and homozygous lmna mutants exhibit prominent skeletal muscle abnormalities during the first week of development. Furthermore, this is the first animal model that potentially implicates Pkc α in muscular laminopathies. This article is protected by copyright. All rights reserved.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping