Modeling Hereditary Spastic Paraplegia (HSP) in Zebrafish

João N. Peres*, Corinne Houart

*Corresponding author for this work

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review


Zebrafish significantly contribute to the study of hereditary spastic paraplegia (HSP) by providing a genetic animal model, amenable to live imaging, for addressing the cellular mechanisms by which known human mutations in spastic paraplegia genes lead to pathology. Loss-of-function studies, using antisense morpholinos of several zebrafish homologs of HSP genes, all show a common phenotype: shortened spinal motor neuron axons, abnormal branching, and reduced motility. These phenotypes are, in the majority of the cases, rescued by the human wild-type mRNA, but not the mutated forms. More importantly, zebrafish have contributed to establishing a novel functional link between the SPG3a gene atlastin and regulation of the bone morphogenetic protein (BMP) signaling activity in motor neurons. Atlastin regulation of endocytosis and trafficking of the BMP receptor BMPR1 provided evidence for the role of signaling pathways in motor neurodegeneration and new possible targets for novel therapeutic approaches.

Original languageEnglish
Title of host publicationMovement Disorders: Genetics and Models: Second Edition
Number of pages7
ISBN (Print)9780124051959
Publication statusPublished - 29 Oct 2014


  • Alsin
  • AT-1
  • Atlastin
  • BMP
  • BMPR1
  • Corticospinal neuron
  • Endocytosis
  • GBA2
  • Hereditary spastic paraplegia
  • HSP
  • Katanin
  • Kif5A
  • Loss-of-function
  • MO
  • Morphants
  • Morpholinos
  • Motor neuron
  • Neurodegeneration
  • NTE
  • Protrudin
  • Spastin
  • Spastizin
  • Spatacsin
  • SPG
  • Strumpellin
  • VPS37A
  • Zebrafish


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