Dataset Information

Loss of ap4s1 in zebrafish leads to neurodevelopmental defects resembling spastic paraplegia 52.

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.

SUBMITTER: D'Amore A

PROVIDER: S-EPMC7187712 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Loss of ap4s1 in zebrafish leads to neurodevelopmental defects resembling spastic paraplegia 52.

D'Amore Angelica A Tessa Alessandra A Naef Valentina V Bassi Maria Teresa MT Citterio Andrea A Romaniello Romina R Fichi Gianluca G Galatolo Daniele D Mero Serena S Battini Roberta R Bertocci Giulia G Baldacci Jacopo J Sicca Federico F Gemignani Federica F Ricca Ivana I Rubegni Anna A Hirst Jennifer J Marchese Maria M Sahin Mustafa M Ebrahimi-Fakhari Darius D Santorelli Filippo M FM

Annals of clinical and translational neurology 20200325 4

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 ...[more]

PMID: 32216065

Dataset Information

Loss of ap4s1 in zebrafish leads to neurodevelopmental defects resembling spastic paraplegia 52.

Publications

Loss of ap4s1 in zebrafish leads to neurodevelopmental defects resembling spastic paraplegia 52.

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