PUBLICATION

Genetic zebrafish models of neurodegenerative diseases

Authors
Bandmann, O., and Burton, E.A.
ID
ZDB-PUB-100525-15
Date
2010
Source
Neurobiology of disease   40(1): 58-65 (Review)
Registered Authors
Bandmann, Oliver, Burton, Edward A.
Keywords
none
MeSH Terms
  • Animals
  • Brain Chemistry/genetics*
  • Disease Models, Animal
  • Genetic Predisposition to Disease/genetics*
  • Humans
  • Models, Genetic*
  • Neurodegenerative Diseases/genetics*
  • Neurodegenerative Diseases/metabolism
  • Neurodegenerative Diseases/pathology
  • Zebrafish/genetics*
PubMed
20493258 Full text @ Neurobiol. Dis.
Abstract
As a consequence of the widespread use of zebrafish in developmental biology studies, an extensive array of experimental tools and techniques has been assembled; it has recently become apparent that these might be exploited in the analysis of human neurodegenerative diseases. A surprising degree of functional conservation has been demonstrated between human genes implicated in neurodegenerative diseases and their zebrafish orthologues. In zebrafish models of recessive Parkinsonism, Parkin or Pink1 knockdown gave rise to specific loss of dopamine neurons; in a zebrafish model of recessive spinal muscular atrophy, loss of Smn1 function caused specific motor axonal defects. In addition, pathological features of several dominant diseases were replicated by transgenic over-expression of mutant human proteins, including Tau, Huntingtin and SOD1. In some cases, conservation of relevant cellular pathways was sufficient that disease-specific post-translational changes to the respective proteins were found in the zebrafish models. These data collectively suggest that the zebrafish can be an appropriate setting in which to model the molecular events underlying human neuropsychiatric disease. Consequently, novel findings yielded by studies in zebrafish models may be applicable to human diseases; this is an exciting prospect, in view of the many potential uses of zebrafish models, for example screening for lead therapeutic compounds, rapid functional assessments of putative modifier genes, and live observation of pathogenic mechanisms in vivo.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping