CORE--MOUSE GENETICS

核心--小鼠遗传学

• 批准号: 7449579
• 负责人: ALLAN C COLLINS
• 金额: $ 9.63万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-01 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7449579
• 关键词: Animal Model; Behavioral; Behavioral Genetics; Biological Assay; Brain; Choline; Cholinergic Receptors; DBA/2 Mouse; Development; Funding; Genes; Genetic; Genetic Models; Human; Inbred C3H Mice; Institutes; Knock-out; Modeling; Mouse Strains; Mus; Mutation; Nicotine; Nicotinic Receptors; Perinatal; Pharmacology; Research; Research Personnel; Schizophrenia; Work; base; congenic; design; human subject; interest; mutant; olfactory bulb; receptor expression; research study; response; sensory gating

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.

小鼠遗传学核心负责在使用遗传定义的小鼠菌株的实验设计和执行中进行协作，以对中心在人类受试者中鉴定出的精神分裂症的遗传和表型方面进行建模。 ACRA7（乙酰胆碱受体α7）是ChRNA7（胆碱能受体烟碱α7）基因的小鼠，用于α7烟碱受体，该中心将集中在人类工作中。实验依赖于ACRA7敲除菌株和ACRA7基因中近交dBA/2小鼠菌株中自发发生的突变。 Sherry Leonard博士（项目0001）建议将ACRA7淘汰 微阵列测定。 Diego Restrepo博士（Project 0002）目前正在研究嗅球灯泡和DBA/2和C3H小鼠之间嗅觉灯泡和嗅觉行为差异中α7烟碱受体表达的差异，这是他将在精神分裂症患者中检查的差异的模型。罗伯特·弗里德曼（Robert Freedman）博士（项目0004）将使用先天小鼠菌株（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无效突变菌株来确定围产期胆碱治疗的作用机理。核心主任艾伦·柯林斯博士， 是行为遗传学研究所的小鼠行为遗传学设施和NIDA资助的研究者的主任，其主要研究兴趣（对尼古丁反应的遗传确定）构成了本应用的动物模型实验的科学基础。