PUBLICATION
Loss of ap4s1 in zebrafish leads to neurodevelopmental defects resembling spastic paraplegia 52
- Authors
- D'Amore, A., Tessa, A., Naef, V., Bassi, M.T., Citterio, A., Romaniello, R., Fichi, G., Galatolo, D., Mero, S., Battini, R., Bertocci, G., Baldacci, J., Sicca, F., Gemignani, F., Ricca, I., Rubegni, A., Hirst, J., Marchese, M., Sahin, M., Ebrahimi-Fakhari, D., Santorelli, F.M.
- ID
- ZDB-PUB-200403-194
- Date
- 2020
- Source
- Annals of clinical and translational neurology 7(4): 584-589 (Journal)
- Registered Authors
- Naef, Valentina, Santorelli, Filippo Maria
- Keywords
- none
- MeSH Terms
-
- Neurodevelopmental Disorders/genetics*
- Neurodevelopmental Disorders/physiopathology*
- Adaptor Protein Complex 4/deficiency
- Adaptor Protein Complex 4/genetics*
- Cohort Studies
- Epilepsy/genetics
- Epilepsy/physiopathology
- Animals
- Adolescent
- Behavior, Animal/physiology
- Male
- Animals, Genetically Modified
- Child, Preschool
- Spastic Paraplegia, Hereditary/genetics*
- Spastic Paraplegia, Hereditary/physiopathology*
- High-Throughput Nucleotide Sequencing
- Disease Models, Animal
- Female
- Humans
- Cerebral Palsy/genetics
- Zebrafish
- PubMed
- 32216065 Full text @ Ann Clin Transl Neurol
Citation
D'Amore, A., Tessa, A., Naef, V., Bassi, M.T., Citterio, A., Romaniello, R., Fichi, G., Galatolo, D., Mero, S., Battini, R., Bertocci, G., Baldacci, J., Sicca, F., Gemignani, F., Ricca, I., Rubegni, A., Hirst, J., Marchese, M., Sahin, M., Ebrahimi-Fakhari, D., Santorelli, F.M. (2020) Loss of ap4s1 in zebrafish leads to neurodevelopmental defects resembling spastic paraplegia 52. Annals of clinical and translational neurology. 7(4):584-589.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping