CORE--MOUSE GENETICS

小鼠遗传学核心负责合作设计和执行实验，这些实验使用基因定义的小鼠品系来模拟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Alpha7)是该中心将在人类工作中重点研究的Alpha7尼古丁受体的CHRNA7(胆碱能受体尼古丁Alpha7)基因的小鼠等价物。这些实验依赖于acra7基因敲除菌株和近交系DBA/2小鼠中acra7基因的自发突变。Sherry Leonard博士(项目0001)建议使用acra7基因敲除作为模型来帮助解释她的人类尸检大脑的结果 微阵列分析。迭戈·雷斯特雷波博士(Project 0002)目前正在研究DBA/2和C3H小鼠嗅球中α7尼古丁受体表达的差异，以及DBA/2和C3H小鼠之间的嗅觉行为差异，以此作为他将在精神分裂症患者中研究差异的模型。Robert Freedman博士(项目0004)将使用同源小鼠品系(C3H背景上的DBA/2 acra7基因座)来研究感觉门控异常的发育药理学。他还将使用各种acra7零突变株来确定围产期胆碱治疗的作用机制。核心主任艾伦·柯林斯博士， 是行为遗传学研究所小鼠行为遗传学设施的主任，也是NIDA资助的研究员，他的主要研究兴趣是确定对尼古丁的反应的基因，形成了这一应用的动物模型实验的科学基础。

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.