PUBLICATION

Ap4s1 truncation leads to axonal defects in a zebrafish model of spastic paraplegia 52

Authors
Li, Y., Zhang, C., Peng, G.
ID
ZDB-PUB-231002-178
Date
2023
Source
International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience   83(8): 753-764 (Journal)
Registered Authors
Peng, Gang, Zhang, Cuizhen
Keywords
AP-4-HSP, SPG52, ap4s1, disease model, zebrafish
MeSH Terms
  • Adaptor Protein Complex 4/genetics
  • Animals
  • Axons/metabolism
  • Disease Models, Animal*
  • Humans
  • Mutation/genetics
  • Spastic Paraplegia, Hereditary*/genetics
  • Zebrafish*/genetics
PubMed
37767851 Full text @ Int. J. Dev. Neurosci.
Abstract
Biallelic mutations in AP4S1, the σ4 subunit of the adaptor protein complex 4 (AP-4), lead to autosomal recessive spastic paraplegia 52 (SPG52). It is a subtype of AP-4-associated hereditary spastic paraplegia (AP-4-HSP), a complex childhood-onset neurogenetic disease characterized by progressive spastic paraplegia of the lower limbs. This disease has so far lacked effective treatment, in part due to a lack of suitable animal models. Here, we used CRISPR/Cas9 technology to generate a truncation mutation in the ap4s1 gene in zebrafish. The ap4s1 truncation led to motor impairment, delayed neurodevelopment, and distal axonal degeneration. This animal model is useful for further research into AP-4 and AP-4-HSP.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping