Genetically Engineered Rodent Care

描述（由申请人提供）：基因工程啮齿动物对于了解整个动物背景下的基因功能至关重要。这对于酒精研究尤其重要，因为我们最终寻求了解单个候选基因对只能在生物体水平上研究的终点的作用，例如，饮酒和酒精诱导的行为反应。 为了满足INIA-West对基因工程动物的需求，该核心将为联合体研究人员提供以下服务。目标1服务将为研究人员提供有关模型开发和结构设计的咨询。目标2的服务都涉及基因靶向小鼠的生产，包括生产靶向载体，胚胎干细胞中的基因靶向，嵌合小鼠的生产，以及建立突变小鼠品系的育种。转基因小鼠服务是目标3的重点。这一目标包括转基因生产，胚胎显微注射，和创始动物的识别。 最后，目标4涉及应用最近开发的锌指核酸酶技术来生产基因敲除大鼠。锌指核酸酶将从商业供应商处购买，该核心将它们注射到大鼠胚胎中，并鉴定所产生的基因靶向大鼠。 公共卫生相关性：酒精的不良影响是我们医疗系统和社会的巨大负担。使用基因工程啮齿类动物允许关于乙醇作用的假设在生物体水平上进行测试。

DESCRIPTION (provided by applicant): Genetically engineered rodents are essential for understanding gene function in the context of the whole animal. This is especially important for alcohol research as we ultimately seek to understand the role of individual candidate genes on endpoints that can only be studied at the organism level, e.g., alcohol drinking and alcohol-induced behavioral responses. To service the needs of the INIA-West for genetically engineered animals, this core will provide the following services to consortium investigators. Aim 1 services will provide consultation to investigators regarding model development and construct design. Aim 2 services all relate to gene targeted mouse production including production of targeting vectors, gene targeting in embryonic stem cells, production of chimerical mice, and breeding to establish mutant mouse lines. Transgenic mouse services are the focus of Aim 3. This aim includes transgene production, embryo microinjection, and identification of founder animals. Lastly, Aim 4 involves the application of recently developed zinc-finger nuclease technology to produce knockout rats. Zinc-finger nucleases will be purchased from a commercial vendor and this core will inject them into rat embryos and identify the gene targeted rats that result. PUBLIC HEALTH RELEVANCE: The adverse effects of alcohol are a tremendous burden on our medical system and on our society. The use of genetically engineered rodents allows hypotheses regarding ethanol action to be tested at the organismal level.