Genetically Engineered Rodent Care

描述(申请人提供)：基因工程啮齿动物对于了解整个动物的基因功能是必不可少的。这对于酒精研究尤其重要，因为我们最终试图了解个体候选基因在只能在有机体水平上研究的终点上的作用，例如酒精饮酒和酒精诱导的行为反应。为了满足INIA-WEST对转基因动物的需求，该核心将为财团调查人员提供以下服务。AIM 1服务将向调查人员提供关于模型开发和结构设计的咨询。目的2所有服务都与基因靶向小鼠生产有关，包括靶向载体的生产，胚胎干细胞的基因靶向，嵌合体小鼠的生产，以及建立突变小鼠系的育种。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鉴定。最后，目标4涉及应用最近开发的锌指核酸酶技术来产生基因敲除大鼠。锌指核酸酶将从商业供应商那里购买，这个核心将把它们注射到大鼠胚胎中，并识别产生的基因靶向大鼠。 与公共健康相关：酒精的不良影响给我们的医疗系统和社会带来了巨大的负担。基因工程啮齿动物的使用使有关乙醇作用的假说能够在生物体水平上得到测试。

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.