The Mouse Genetics Core is responsible for collaborating in the design and execution of experiments that use genetically-defined mouse strains to model the genetic and phenotypic aspects of schizophrenia that the Center has identified in human subjects. Acra7 (acetylcholine receptor alpha7) is the mouse equivalent of the CHRNA7 (CHolinergic Receptor Nicotinic alpha7) gene for the alpha7 nicotinic receptor that the Center will be focusing on in their human work. The experiments rely on acra7 knockout strains and a spontaneously occurring mutation in the inbred DBA/2 mouse strain in the acra7 gene. Dr. Sherry Leonard (Project 0001) proposes to use acra7 knockouts as a model to help interpret results from her human post mortem brainmicroarray assays. Dr. Diego Restrepo (Project 0002) is currently examining differences in alpha7 nicotinic receptor expression in the olfactory bulb and olfactory behavioral differences between DBA/2 and C3H mice, as a model for the differences he will be examining in schizophrenics. Dr. Robert Freedman (Project 0004) will use congenic mouse strains (the DBA/2 acra7 locus on a C3H background) to investigate the developmental pharmacology of sensory gating abnormalities. He will also use various acra7 null mutant strains to determine the mechanisms of action of perinatal choline treatment. The director of the core, Dr. Allan Collins,is director of the mouse behavioral genetics facility at the Institute for Behavioral Genetics and a NIDA-funded investigator whose principal research interest, the genetic determination of the response to nicotine, formed the scientific basis of the animal model experiments of this application.
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