Gene-environment interactions in the pathogenesis of autism-like neurodevelopmental damage: a mouse model
Johns Hopkins University
Autism likely results from a combination of genetic and environmental factors, as particular genetic variations may make an individual more sensitive to environmental factors. The present study will examine the interaction between a specific gene and an environmental factor, both known to confer risk of neurodevelopmental problems. The gene under study is DISC1, which is located in a region of the human genome likely to harbor an autism susceptibility gene. Mice with mutant versions of this gene have a predisposition to neurodevelopmental problems, which may be exacerbated or influenced by environmental factors. One prenatal environmental factor that may modulate vulnerability to autism in the prenatal period is the maternal immune response. In this study, Dr. Pletnikov and colleagues will examine the interaction between mutations in DISC1 and the maternal immune response. They will administer a compound which mimics important aspects of the maternal immune response to viral infections to pregnant mice which harbor mutant versions of DISC1. They will examine neural development and autistic-like behaviors in the offspring of mice given the immune stimulus during pregnancy to test the hypothesis that the environmental challenge (immune activation) will exacerbate the alterations in brain development and behavior seen in DISC1 mutants,. This research may identify molecular mechanisms mediating gene-environment interactions important for neurodevelopment, which would be therefore be novel targets for the development of drugs to prevent or treat neurodevelopmental problems.