CORE--MOUSE GENETICS

小鼠遗传学核心负责合作设计和执行实验，这些实验使用遗传学定义的小鼠品系来模拟该中心在人类受试者中确定的精神分裂症的遗传和表型方面。Acra 7（乙酰胆碱受体α 7）是CHRNA 7（胆碱能受体烟碱α 7）基因的小鼠等价物，用于α 7烟碱受体，该中心将在其人类工作中重点关注。这些实验依赖于acra 7敲除品系和acra 7基因中近交DBA/2小鼠品系中自发发生的突变。Sherry伦纳德博士（项目0001）建议使用acra 7敲除作为模型，以帮助解释她的人类死后大脑的结果 微阵列分析。Diego Restrepo博士（项目0002）目前正在研究DBA/2和C3 H小鼠嗅球中α 7烟碱受体表达的差异和嗅觉行为差异，作为他将在精神分裂症患者中研究的差异模型。Dr. Robert Freedman（项目0004）将使用同类小鼠品系（C3 H背景上的DBA/2 acra 7位点）研究感觉门控异常的发育药理学。他还将使用各种acra 7无效突变菌株来确定围产期胆碱治疗的作用机制。核心的主任艾伦柯林斯博士， 是行为遗传学研究所的小鼠行为遗传学机构的主任，也是NIDA资助的研究员，其主要研究兴趣是尼古丁反应的遗传测定，形成了本申请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.