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Please use this identifier to cite or link to this item: http://hdl.handle.net/1807/18335

Title: Disc1 Mutant Mice Subjected to Chronic Social Defeat Stress as a Model of Gene-Environment Interaction in Schizophrenia and Depression
Authors: Haque, F. Nipa
Advisor: Wong, Albert Hung Choy
Department: Pharmacology
Keywords: gene-environment interaction
social defeat
Disc1 mutant mice
schizophrenia
depression
animal model
disrupted-in-schizophrenia 1 (Disc1)
brain-derived neurotrophic factor (Bdnf)
phosphodiesterase 4b (Pde4b)
valproate
histone deacetylase (HDAC)
epigenetics
Q31L
L100P
Issue Date: 25-Jan-2010
Abstract: 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.
URI: http://hdl.handle.net/1807/18335
Appears in Collections:Master
Department of Pharmacology and Toxicology - Master theses

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