Behavioral aspects of NRG1 hypomorphic mice

Columbia University Health Sciences, New York NY

Investigators

Abstract

[unreadable] DESCRIPTION (provided by applicant): Neuregulin-1 (NRG1) has been identified as a schizophrenia susceptibility gene using linkage and haplotype analysis. NRG1 protein is a cell-cell signaling molecule involved in numerous CNS activities that fit tightly with current hypotheses regarding the neurobiological basis of schizophrenia. Mice with reduced NRG1 activity (NRG1 hypomorphs) display behaviors that are relevant to the positive symptoms of schizophrenia. However, animal models that recapitulate the negative symptoms (social deficits, poor attention) of schizophrenia are scarce. This research will examine: 1) whether NRG1 hypomorphic mice display the social deficit endophenotype seed in schizophrenia; 2) Do NRG1 hypomorphic mice exhibit defects in olfactory function; 3) Do structural alterations in the olfactory bulb correlate with poor olfactory function and social deficits in NRG1 hypomorphic mice. The underlying hypothesis of these experiments is that defective neurodevelopment in the olfactory bulb of NRG1 hypomorphic mice results in defective olfactory function that directly influences social behavior. This research is intended to provide a mouse model for the negative symptoms of schizophrenia as well as a plausible mechanism for the social deficit endophenotype. [unreadable] [unreadable]