Aggressive-like behavior and increased glycine transporters in a zebrafish model of CHARGE syndrome

Liu, H., Liu, Z.Z.
Behavioural brain research   378: 112293 (Journal)
Registered Authors
CHARGE syndrome, aggressive-like behavior, chd7 heterozygous zebrafish mutants, glycine, glycine transporters
MeSH Terms
  • Aggression/drug effects
  • Aggression/physiology*
  • Animals
  • Animals, Genetically Modified
  • Behavior, Animal/drug effects
  • Behavior, Animal/physiology*
  • Behavioral Symptoms/drug therapy
  • Behavioral Symptoms/etiology
  • Behavioral Symptoms/physiopathology*
  • Brain/drug effects
  • Brain/metabolism*
  • CHARGE Syndrome/complications*
  • Cycloserine/pharmacology
  • DNA Helicases/genetics
  • DNA-Binding Proteins/genetics
  • Disease Models, Animal
  • Glycine Plasma Membrane Transport Proteins/antagonists & inhibitors
  • Glycine Plasma Membrane Transport Proteins/metabolism*
  • Heterozygote
  • Sarcosine/pharmacology
  • Zebrafish
  • Zebrafish Proteins/genetics
31610215 Full text @ Behav. Brain Res.
Coloboma, heart defects, choanal atresia, restricted growth and development, genital hypoplasia, ear abnormalities and/or hearing loss (CHARGE) syndrome is a congenital disorder that is mainly caused by mutations within chromodomain helicase DNA-binding protein 7 (chd7). Behavioral abnormalities have been addressed in CHARGE syndrome, but the underlying mechanisms are still poorly understood. Here, we performed four behavioral tests-including the open-field test, novel-tank test, shoaling test and mirror-induced attack test-in chd7 heterozygous zebrafish mutants in order to characterize the behavioral abnormalities in a zebrafish model of CHARGE syndrome. We found that chd7 heterozygous mutants exhibited anxious-like behavior and aggressive-like behavior in the open-field test and in the mirror-induced attack test, respectively, which resembled the reported behavioral abnormalities in CHARGE syndrome in humans. Moreover, we found that glycine and D-cycloserine treatment rescued the aggressive behavior of chd7 heterozygous zebrafish mutants, indicating that the excitation and inhibition balance might be disrupted in the brains of chd7 heterozygous zebrafish mutants. Further analysis showed that the expression of glycine transporters was dramatically increased in the brains of chd7 heterozygous zebrafish mutants. Treatment with an inhibitor of glycine transporter 1, sarcosine, partially rescued the aggressive-like behavior of chd7 heterozygous zebrafish mutants. Taken together, our data suggest that the aggressive behavior in CHARGE syndrome may be due to the increased expression of glycine transporters, and inhibition of the activity of glycine transporters may be an approach to treat the behavioral abnormalities in CHARGE syndrome.
Genes / Markers
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Engineered Foreign Genes
Errata and Notes