Return to search

Disc1 Mutant Mice Subjected to Chronic Social Defeat Stress as a Model of Gene-Environment Interaction in Schizophrenia and Depression

Human genetic data suggests DISC1 (Disrupted-in-schizophrenia 1) is a susceptibility gene for schizophrenia and depression. Disc1 Q31L-/- mutants show depression-like behaviour and Disc1 L100P-/- mutants schizophrenia-like behaviour. Heterozygous mutants show an intermediate phenotype. In a gene-environment interaction study, we exposed heterozygotes to chronic social defeat (CSD) stress and phenotyped behaviour. Disc1, Bdnf(III) and Pde4b mRNA levels were also measured. Moreover, as epigenetic mechanisms may mediate some effects of CSD, we also exposed wildtype mice to CSD concurrently with the histone deacetylase inhibitor valproate. We found that CSD increased anxiety in L100P-/+ mutants, and that levels of Disc1, Bdnf(III) and Pde4b mRNA were higher in this mutant. Valproate treatment did not correct CSD-induced behavioural changes. In conclusion, we have demonstrated an interaction between a strong susceptibility gene for psychiatric disease and an environmental manipulation similar to stressors known to affect mental illness.

Identiferoai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/18335
Date25 January 2010
CreatorsHaque, F. Nipa
ContributorsWong, Albert Hung Choy
Source SetsUniversity of Toronto
Languageen_ca
Detected LanguageEnglish
TypeThesis

Page generated in 0.0021 seconds