Related Experiment Video
Updated: Jul 29, 2026
11:27
Efficient Production and Identification of CRISPR/Cas9-generated Gene Knockouts in the Model System Danio rerio
Published on: August 28, 2018
21.9K
CHCHD10P80L knock-in zebrafish display a mild ALS-like phenotype
Virginie Petel Légaré1, Ziyaan A Harji1, Christian J Rampal1
1Department of Neurology and Neurosurgery, Montreal Neurological Institute, Faculty of Medicine, McGill University, Canada.
Experimental Neurology
|September 11, 2024
Summary
Mutations in the CHCHD10 gene cause neurodegenerative diseases like ALS. A zebrafish model of the CHCHD10 P80L variant showed motor deficits and reduced survival, suggesting a conserved disease mechanism.
Area of Science:
- Neuroscience
- Genetics
- Mitochondrial Biology
Background:
- Mutations in the nuclear-encoded mitochondrial gene CHCHD10 are linked to amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD).
- Understanding the pathogenic mechanisms of CHCHD10 variants is crucial for developing therapeutic strategies.
Purpose of the Study:
- To investigate the pathogenicity of the ALS-associated CHCHD10 P80L variant.
- To establish and characterize a zebrafish (Danio rerio) knock-in (KI) model expressing the Chchd10 P83L variant.
Main Methods:
- Generated a zebrafish KI model expressing the Chchd10 P83L variant.
- Assessed motor function, survival rates, neuromuscular junction (NMJ) integrity, muscle cell morphology, and motor neuron counts.
- Performed bulk RNA sequencing on spinal cord tissue to analyze transcriptional changes.
Main Results:
- Larval chchd10 P83L/P83L fish exhibited motor impairment, reduced survival, and abnormal NMJs.
- Adult chchd10 P83L/P83L zebrafish showed reduced muscle cell size and fewer motor neurons compared to controls.
- Transcriptional analysis revealed neuroinflammation, apoptosis, and mt-DNA inflammatory responses in the model.
Conclusions:
- The CHCHD10 P83L variant confers an ALS-like phenotype in zebrafish.
- The zebrafish model recapitulates key pathological features of CHCHD10-associated neurodegeneration.
- Findings suggest conserved mechanisms underlying CHCHD10-related motor neuron diseases.
Related Concept Videos
01:29Alzheimer Disease l: Introduction
Alzheimer disease is a chronic, progressive, and irreversible neurodegenerative disorder and the most common cause of dementia in older adults. It leads to gradual neuronal loss, causing cognitive decline, behavioral changes, and loss of functional independence.Risk Factors and EtiologyThe disease is multifactorial. Age is the strongest risk factor, with prevalence doubling every 5 years after age 65. Genetic factors include mutations in genes such as APP, PSEN1, and PSEN2, which are associated...
01:21Huntington Disease l: Introduction
Huntington disease or HD is a progressive, fatal neurodegenerative disorder inherited in an autosomal dominant pattern.PathophysiologyIt is caused by expansion of the CAG trinucleotide repeat in the HTT gene on chromosome 4 (4p16.3), producing an abnormal huntingtin protein with an expanded polyglutamine tract. This misfolded protein disrupts cellular function, leading to neuronal death. Normal alleles have ≤26 repeats, 27–35 are intermediate (risk of expansion), 36–39 show reduced penetrance,...