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
-
- Cerebral Palsy/genetics
- Animals, Genetically Modified
- Child, Preschool
- Female
- Epilepsy/genetics
- PubMed
- 32216065 Full text @ Ann Clin Transl Neurol
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