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Loss of ap4s1 in zebrafish leads to neurodevelopmental defects resembling spastic paraplegia 52
- Source :
- Annals of Clinical and Translational Neurology, Annals of Clinical and Translational Neurology, Vol 7, Iss 4, Pp 584-589 (2020)
- Publication Year :
- 2020
- Publisher :
- John Wiley and Sons Inc., 2020.
-
Abstract
- Autosomal recessive spastic paraplegia 52 is caused by biallelic mutations in AP4S1 which encodes a subunit of the adaptor protein complex 4 (AP‐4). Using next‐generation sequencing, we identified three novel unrelated SPG52 patients from a cohort of patients with cerebral palsy. The discovered variants in AP4S1 lead to reduced AP‐4 complex formation in patient‐derived fibroblasts. To further understand the role of AP4S1 in neuronal development and homeostasis, we engineered the first zebrafish model of AP‐4 deficiency using morpholino‐mediated knockdown of ap4s1. In this model, we discovered several phenotypes mimicking SPG52, including altered CNS development, locomotor deficits, and abnormal neuronal excitability.
- Subjects :
- 0301 basic medicine
Male
Adolescent
Protein subunit
Adaptor Protein Complex 4
Neurosciences. Biological psychiatry. Neuropsychiatry
Brief Communication
Cerebral palsy
Animals, Genetically Modified
Cohort Studies
03 medical and health sciences
0302 clinical medicine
Spastic
Medicine
Animals
Humans
RC346-429
Zebrafish
Gene knockdown
Epilepsy
biology
Behavior, Animal
business.industry
Spastic Paraplegia, Hereditary
General Neuroscience
Cerebral Palsy
Signal transducing adaptor protein
High-Throughput Nucleotide Sequencing
medicine.disease
biology.organism_classification
Phenotype
Cell biology
Disease Models, Animal
030104 developmental biology
Neurodevelopmental Disorders
Child, Preschool
Female
Neurology (clinical)
Neurology. Diseases of the nervous system
business
Paraplegia
Brief Communications
030217 neurology & neurosurgery
RC321-571
Subjects
Details
- Language :
- English
- ISSN :
- 23289503
- Volume :
- 7
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- Annals of Clinical and Translational Neurology
- Accession number :
- edsair.doi.dedup.....dc0bac310e1eef3e88abdecf1712a2c9