PUBLICATION

A genetic model of amyotrophic lateral sclerosis in zebrafish displays phenotypic hallmarks of motoneuron disease

Authors
Ramesh, T., Lyon, A.N., Pineda, R.H., Wang, C., Janssen, P.M., Canan, B.D., Burghes, A.H., and Beattie, C.E.
ID
ZDB-PUB-100601-15
Date
2010
Source
Disease models & mechanisms   3(9-10): 652-662 (Journal)
Registered Authors
Beattie, Christine, Pineda, Ricardo, Wang, Chunping
Keywords
none
MeSH Terms
  • Amino Acid Substitution/genetics
  • Amyotrophic Lateral Sclerosis/genetics*
  • Animals
  • Animals, Genetically Modified
  • Atrophy
  • Disease Models, Animal
  • Larva/metabolism
  • Models, Genetic*
  • Motor Neuron Disease/genetics*
  • Motor Neuron Disease/pathology*
  • Motor Neurons/pathology
  • Muscle Contraction
  • Muscles/pathology
  • Muscles/physiopathology
  • Mutation/genetics
  • Neuromuscular Junction/pathology
  • Phenotype
  • Superoxide Dismutase/genetics
  • Superoxide Dismutase/metabolism
  • Survival Analysis
  • Zebrafish/genetics*
(all 21)
PubMed
20504969 Full text @ Dis. Model. Mech.
Abstract
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder that, for ~80% of patients, is fatal within five years of diagnosis. To better understand ALS, animal models have been essential; however, only rodent models of ALS exhibit the major hallmarks of the disease. Here, we report the generation of transgenic zebrafish overexpressing mutant Sod1. The construct used to generate these lines contained the zebrafish sod1 gene and ~16 kb of flanking sequences. We generated lines expressing the G93R mutation, as well as lines expressing wild-type Sod1. Focusing on two G93R lines, we found that they displayed the major phenotypes of ALS. Changes at the neuromuscular junction were observed at larval and adult stages. In adulthood the G93R mutants exhibited decreased endurance in a swim tunnel test. An analysis of muscle revealed normal muscle force, however, at the end stage the fish exhibited motoneuron loss, muscle atrophy, paralysis and premature death. These phenotypes were more severe in lines expressing higher levels of mutant Sod1 and were absent in lines overexpressing wild-type Sod1. Thus, we have generated a vertebrate model of ALS to complement existing mammal models.
Genes / Markers
Figures
Figure Gallery (7 images)
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Expression
Phenotype
Fish Conditions Stage Phenotype Figure
os10Tgstandard conditionsDays 7-13
os10Tgstandard conditionsAdult
os10Tgstandard conditionsAdult
os10Tgstandard conditionsAdult
os10Tgstandard conditionsAdult
os10Tgstandard conditionsAdult
os10Tgstandard conditionsAdult
os10Tgstandard conditionsAdult
os10Tgstandard conditionsAdult
os10Tgstandard conditionsAdult
1 - 10 of 13
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Mutations / Transgenics
Allele Construct Type Affected Genomic Region
os3TgTransgenic Insertion
    os4TgTransgenic Insertion
      os6TgTransgenic Insertion
        os10TgTransgenic Insertion
          1 - 4 of 4
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          Human Disease / Model
          Human Disease Fish Conditions Evidence
          amyotrophic lateral sclerosisos10Tgstandard conditionsTAS
          amyotrophic lateral sclerosisos6Tgstandard conditionsTAS
          1 - 2 of 2
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          Sequence Targeting Reagents
          No data available
          Fish
          Fish
          os3Tg
          os4Tg
          os6Tg
          os10Tg
          WT
          1 - 5 of 5
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          Antibodies
          Orthology
          Engineered Foreign Genes
          Marker Marker Type Name
          DsRedEFGDsRed
          1 - 1 of 1
          Show
          Mapping
          No data available
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          Citation
          Ramesh, T., Lyon, A.N., Pineda, R.H., Wang, C., Janssen, P.M., Canan, B.D., Burghes, A.H., and Beattie, C.E. (2010) A genetic model of amyotrophic lateral sclerosis in zebrafish displays phenotypic hallmarks of motoneuron disease. Disease models & mechanisms. 3(9-10):652-662.