Enhancing Animal Care in a New High-Throughput Rodent Behavior Analysis Core Facility

 人类遗传学和基因组编辑的快速发展为开发不同人类疾病的动物模型创造了前所未有的科学机会。然而，这些机会已经严重地使哥伦比亚大学医学中心的动物设施紧张起来。本申请反映了CNOC对提高动物护理和福利质量的坚定承诺，以满足或超过PHS关于实验动物护理和使用的政策。由于预期集中在神经系统疾病方面的努力，该项目侧重于疾病研究的神经生物学及其转化，以促进人类健康，将升级和装备现有CNOC动物设施内的1，365平方英尺区域，作为建立高通量啮齿动物行为分析核心的努力的一部分。这一改进后的设施将包括专门用于啮齿动物饲养的屏障空间、活体动物手术和病毒载体注射的动物准备和性能以及行为测试。具体而言，该提案寻求联邦资金，用于购买三个单层和四个双层HEPA过滤通风笼架，四个HEPA过滤通风更换和转运站，以及一个生物安全柜。还将寻求与安装和连接通风架和生物安全柜有关的相关建筑费用。我们在这里建立的设施将使CNOC研究人员能够抓住遗传学和基因组工程进步所创造的机会，同时仍然提供最高标准的动物护理和福利以及人类安全。与此保持一致，所要求的设备将使我们能够满足三个具体的要求。 目的：（1）尽量增加鼠笼的容量;（2）尽量减低环境改变对动物行为的影响，以及在更换笼舍及进行动物实验操作时，尽量减低人类接触鼠类过敏原及破坏鼠群生物安全的风险;以及（3）允许存活手术的无菌性能和将病毒载体安全注射到动物体内以实现最佳质量的研究。该提案代表了CNOC的关键和实质性的努力，以满足其疾病社区的神经生物学的当前和预期的需求，为啮齿动物（主要是小鼠）提供一个新的和功能齐全的屏障行为测试设施。认识到这一努力的重要性，院长办公室、哥伦比亚转化神经科学倡议和基因组医学研究所已经走到一起，共同提供所有必要的支持，以创建上述设施，超出了这笔赠款将提供的资源。这一机构承诺将包括：（1）将新设施的翻新/建设成本纳入正在进行的旨在升级其动物护理设施的比较医学研究所的资本项目，以及（2）支付所有行为测试设备的购买费用。

 DESCRIPTION (provided by applicant): Rapid advances in human genetics and in genome editing are creating unprecedented scientific opportunities to develop animal models of different human diseases. These opportunities, however, are already severely straining the animal facilities at Columbia University Medical Center (CUMC). This application reflects the deep commitment of the CUMC to improving the quality of animal care and welfare necessary to meet or exceed PHS Policy on the Care and Use of Laboratory Animals. Because of the expected concentration of efforts in neurological disorders, this project, which focuses on neurobiology of disease research and its translation to advance human health, will upgrade and equip a 1,365 square foot area within the existing CUMC animal facility as part of an effort to establish a high-throughput rodent behavior analysis core. This improved facility will be comprised of barrier-space for dedicated rodent housing, animal preparation for and performance of live animal surgery and viral vector injections, and behavioral testing. Specifically, the proposal seeks Federal funds for the purchase of three single and four double HEPA-filtered ventilated cage racks, four HEPA-filtered ventilated changing and transfer stations, and one biosafety cabinet. Associated construction costs related to the installation and connection of the ventilated racks and the biosafety cabinet will also be sought. The facility we establish here will allow CUMC investigators to seize the opportunities created by advances in genetics and genome engineering, while still providing for the very highest standards of animal care and welfare and human safety. In keeping with this, the requested equipment will allow us to fulfill three Specific Aims: (1) to maximize the dedicated rodent housing capacity; (2) to minimize the effects of environmental changes on animal behaviors and to minimize the risk of harmful human exposure to rodent allergens and breaks in colony biosecurity during cage changes and experimental manipulation of animals; and, (3) to allow the sterile performance of survival surgery and safe injection of viral vectors into animals to achieve optimal quality research. This proposal represents CUMC's critical and substantial effort to meet the present and anticipated needs of its neurobiology of disease community by providing a new and fully-functional barrier behavioral testing facility for rodents (primarily mice). Recognizing the importance of this effort the Dean's office, the Columbia Translational Neuroscience Initiative, and the Institute of Genomic Medicine have come together to collectively provide all of the necessary support to create the facility described above beyond the resource that this grant would provide. This institutional commitment will include: (1) integrating the costs of renovation/construction of the new facility into the ongoing capital project of CUMC's Institute of Comparative Medicine aimed at upgrading its animal care facilities and (2) covering the purchase of all of the behavior testin apparatii.