2014 Grant Recipient – Brian Grone

• Mutations in the synaptic gene STXBP1 are linked to childhood epilepsies and neurodevelopmental disorders, including LGS
• Zebrafish STXBP1 homologs (stxbp1a and stxbp1b) are highly conserved and expressed in the larval zebrafish brain.
• These new zebrafish mutant lines successfully recapitulate clinical phenotypes associated with human STXBP1 mutations.
  • Profound lack of movement.
  • Low electrical brain activity.
  • Low heart rate.
  • Decreased glucose and mitochondrial metabolism.
  • Early fatality.
  • Spontaneous electrographic seizures.
  • Reduced locomotor activity response to a “dark-flash” visual stimulus.
  • Normal metabolism, heart rate, survival, and baseline locomotor activity.

Results:

Epilepsy, Behavioral Abnormalities, and Physiological Comorbidities in Syntaxin-Binding Protein 1 (STXBP1) Mutant Zebrafish

Lay Abstract:

Mutations in the human syntaxin-binding protein 1 (STXBP1) gene are associated with a range of clinical outcomes. They were first identified in children with early infantile epileptic encephalopathy and subsequently found in patients diagnosed with other forms of epileptic encephalopathy including infantile spasms, Lennox-Gastaut Syndrome, and Dravet Syndrome. Despite progress in understanding basic functions of STXBP1, exploring the consequences of these mutations would benefit from well-characterized animal models. Zebrafish are a leading organism with which to model human neurological disease and epilepsy in particular. We will use zebrafish as a model for LGS as we explore in more detail the impact of STXBP1 mutations.

Updated 05/06/26 (KK)