ZFIN ID: ZDB-PUB-190125-15
A zebrafish model to study small-fiber neuropathy reveals a potential role for GDAP1
Eijkenboom, I., Vanoevelen, J.M., Hoeijmakers, J.G.J., Wijnen, I., Gerards, M., Faber, C.G., Smeets, H.J.M.
Date: 2019
Source: Mitochondrion   47: 273-281 (Journal)
Registered Authors:
Keywords: Fission, Fusion, Mitochondrial dynamics, Sensory neurites, Small-fiber neuropathy, Zebrafish
MeSH Terms:
  • Animals
  • Disease Models, Animal
  • Humans
  • Mitochondria/genetics
  • Mitochondria/metabolism*
  • Mitochondria/pathology
  • Mitochondrial Dynamics*
  • Nerve Tissue Proteins/genetics
  • Nerve Tissue Proteins/metabolism*
  • Peripheral Nervous System Diseases/genetics
  • Peripheral Nervous System Diseases/metabolism*
  • Peripheral Nervous System Diseases/pathology
  • Zebrafish/genetics
  • Zebrafish/metabolism*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed: 30677530 Full text @ Mitochondrion
Mutations in genes involved in mitochondrial dynamics (fusion and fission) have been implicated in many peripheral neuropathies. We hypothesized that defects in these genes could result in a phenotype resembling features of small-fiber neuropathy (SFN). This was investigated in zebrafish by knocking down two genes involved in mitochondrial dynamics gdap1 (possibly fission and motility) and opa1 (fusion) using established morpholinos. Our read-outs were nerve density in the caudal fin and a behavioral response to temperature changes, both based on comparable hallmarks of SFN in patients. Knockdown of gdap1 resulted in zebrafish embryos with a reduced density of sensory neurites compared to control morpholino-injected embryos. Furthermore, these embryos demonstrated a decreased temperature-related activity. In contrast, a knockdown of opa1 did not affect the density of sensory neurites nor the temperature-related activity. However, only the opa1 morphants had an effect on mitochondrial network morphology. As we were not able to visualize the mitochondria in the neurons, it could well be that changes in the mitochondrial network remained undetected. Our data indicate that GDAP1 knockdown affects sensory neurite development, although it is unclear if a problem in mitochondrial fission and network formation is the pathophysiological mechanism. Although we did not observe an effect of inhibiting mitochondrial fusion during development, we still propose that genes involved in mitochondrial dynamics should be screened for mutations in patients with SFN.