CORE--MOUSE GENETICS

小鼠遗传学核心负责合作设计和执行实验，使用基因定义的小鼠品系来模拟该中心在人类受试者中发现的精神分裂症的遗传和表型方面。Acra7（乙酰胆碱受体α 7）是CHRNA7（胆碱能受体烟碱α 7）基因的小鼠等效物，该中心将在其人类工作中重点研究α 7烟碱受体。实验依赖于acra7基因敲除菌株和自交系DBA/2小鼠菌株中自发发生的acra7基因突变。Dr. Sherry Leonard （Project 0001）建议使用acra7敲除作为模型来帮助解释她的人类死后大脑的结果

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 brain microarray 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.