ZFIN ID: ZDB-PUB-160811-2
DNA methylation regulates gabrb2 mRNA expression: Developmental variations and disruptions in L-Methionine-induced zebrafish with schizophrenia-like symptoms
Wang, L., Jiang, W., Lin, Q., Zhang, Y., Zhao, C.
Date: 2016
Source: Genes, brain, and behavior   15(8): 702-710 (Journal)
Registered Authors: Lin, Qing, Zhang, Yiyue
Keywords: GABAergic system, MET, behavioral deficits, developmental variations, gabrb2, genome-wide DNA methylation, mRNA expression, promoter DNA methylation, schizophrenia, zebrafish
MeSH Terms:
  • Animals
  • DNA Methylation*
  • Disease Models, Animal
  • Gene Expression Regulation
  • Genetic Predisposition to Disease
  • Methionine
  • Polymorphism, Single Nucleotide
  • Promoter Regions, Genetic
  • RNA, Messenger/biosynthesis
  • RNA, Messenger/genetics*
  • Receptors, GABA/genetics*
  • Receptors, GABA/metabolism
  • Schizophrenia/chemically induced
  • Schizophrenia/genetics*
  • Schizophrenia/metabolism
  • Zebrafish
  • gamma-Aminobutyric Acid/metabolism
PubMed: 27509263 Full text @ Genes Brain Behav.
Single nucleotide polymorphisms (SNPs) in the human type A gamma-aminobutyric acid (GABA) receptor β2 subunit gene (GABRB2) have been associated with schizophrenia and quantitatively correlated with mRNA expression in the postmortem brain tissue of patients with schizophrenia. l-Methionine (MET) administration has been reported to cause a recrudescence of psychotic symptoms in patients with schizophrenia, and similar symptoms have been generated in MET-induced mice. In this study, a zebrafish animal model was used to evaluate the relationship between the gabrb2 mRNA expression and its promoter DNA methylation in developmental and MET-induced schizophrenia-like zebrafish. The results indicated developmental increases in global DNA methylation and decreases in gabrb2 promoter methylation in zebrafish. A significant increase in gabrb2 mRNA levels was observed after GABA was synthesized. Additionally, the MET-triggered schizophrenia-like symptoms in adult zebrafish, involving social withdrawal and cognitive dysfunction analyzed with social interaction and T-maze behavioral tests, were accompanied by significantly increased DNA methylation levels in the global genome and the gabrb2 promoter. Furthermore, the significant correlation between gabrb2 mRNA expression and gabrb2 promoter methylation observed in the developmental stages became non-significant in MET-triggered adult zebrafish. These findings demonstrate that gabrb2 mRNA expression is associated with DNA methylation varies by developmental stage and show that these epigenetic association mechanisms are disrupted in MET-triggered adult zebrafish with schizophrenia-like symptoms. In conclusion, these results provide plausible epigenetic evidence of the GABAA receptor β2 subunit involvement in the schizophrenia-like behaviors and demonstrate the potential use of zebrafish models in neuropsychiatric research.