Preclinical Models Core

(核心F-PMC：临床前模型核心) 项目总结 描述：临床前模型核心(PMC)支持研究IDD病理生理学和/或IDD的IDDRC用户 使用以下两种临床前模型中的一种或两种寻找IDD的新治疗方法：(1)啮齿动物模型：这一核心 组件帮助用户描述遗传性或非遗传性的小鼠模型的行为表型。 后天残疾。这一核心评估的主要行为领域包括：学习、记忆、社交 偏好、沟通、运动功能和情感障碍相关行为；(2)人类IPSC模型： 该核心组件通过生成诱导多能干细胞来帮助用户创建IDD的细胞模型 (IPSC)使用标准重新编程技术或通过CRISPR-Cas9 ESTABLISD进行基因组编辑 IPSC系，然后分化为分子和细胞表型感兴趣的神经细胞类型 人物刻画。这些细胞，其中一些来自患有IDDS的人类，提供了一种可能的模型 仔细研究遗传病的分子和细胞后果，并评估可能的疗效 治疗。许多中心调查人员正在使用互补的模型系统，这两个 服务在一个领导下密切互动。 PMC强调对用户及其工作人员的培训。训练有素的用户可以在自己的实验室继续研究， 或者他们可以以更低的成本利用PMC中的设备和/或试剂。PMC提供的服务 是对所有其他中心核心所提供的核心的补充，并且用户经常使用不止一个 核心来完成一个项目。此外，私营部门委员会与姊妹国际数据中心的类似核心密切互动，以分享 协议，交叉验证结果衡量标准，以提高国际发展研究中心的严谨性和可重复性 网络。 与IDDRC任务的相关性：PMC在所有三个领域之间架起了桥梁，这三个领域的主题是 印章/宾夕法尼亚IDDRC(见总体研究计划)。核心是根据用户调查而开发的 在2014年，它强调了需要一个以缺碘为重点的机构来研究与缺碘相关的行为和细胞 在IDD临床症状背景下的表型并利用IPSC潜力获得洞察力 致力于疾病病理生理学，并与该中心的其他核心合作改进IDDS的治疗 IDDRC。 资格：这些服务既适用于北卡罗来纳州/宾夕法尼亚州国际发展研究中心的批准用户，也适用于 网络中的其他中心。

(CORE F – PMC: PRECLINICAL MODELS CORE) PROJECT SUMMARY Description: The Preclinical Models Core (PMC) supports IDDRC users who study IDD pathophysiology and/or seek new treatments for IDD using one or both of the following preclinical models: (1) Rodent models: This Core component assists users with the characterization of behavioral phenotypes in mouse models of genetic or acquired disabilities. Major behavioral domains assessed in this core include: learning, memory, social preference, communication, motor function, and affective disorder-related behaviors; (2) Human iPSC models: This Core component assists users to create cell models of IDD by generating induced pluripotent stem cells (iPSCs) using standard reprogramming technologies or by genome editing via CRISPR-Cas9 on established iPSC lines, followed by differentiation into neural cell types of interest for molecular and cellular phenotype characterization. These cells, some derived from humans with IDDs, provide a model in which it is possible to scrutinize molecular and cellular consequences of genetic disease and to evaluate the efficacy of possible therapies. The complementary model systems are being used by many of the center investigators, and the two services interact closely under one leadership. The PMC emphasizes training of users and their staff. Trained users can continue studies in their own laboratory, or they can utilize the equipment and/or reagents in the PMC at reduced cost. The services offered by the PMC are complementary to those offered by all of the other center cores, and users frequently use more than one core to complete a project. In addition, the PMC interacts closely with similar cores at sister IDDRCs to share protocols, cross-validate outcome measures, in order to improve rigor and reproducibility across the IDDRC network. Relevance to IDDRC Mission: The PMC bridges all three domains of “Genes, Brain, and Behavior”, the theme of the CHOP/Penn IDDRC (see Research Plan Overall). The Core was developed in response to a user survey in 2014 that emphasized a need for an IDD-focused facility to study IDD-related behavioral and cellular phenotypes in the context of IDD clinical symptoms and to take advantage of the iPSC potentials to gain insights into disease pathophysiology and improve treatment for IDDs in a collaborative manner with other Cores of this IDDRC. Eligibility: These services are available both to approved users of the IDDRC at CHOP/Penn and to users at other Centers in the Network.