The Jackson Laboratory KOMP2 Phenotyping Center

描述（由申请人提供）：Jackson实验室（JAX）很好地定位于作为KOMP2研究网络的成员充分参与，并支持其目标，建立一个了解哺乳动物基因功能的全球资源。JAX是小鼠遗传学和人类疾病小鼠模型开发的领先中心。凭借深厚的积累知识和杰克逊实验室科学家独特的专业知识，我们已经组建了必要的领导团队，并为具有成本效益的JAX KOMP2表型中心创建了蓝图，该中心将对KOMP菌株进行高质量的功能评估。JAX在众多先前资助的高通量表型项目中展示的经验和成功证明为我们提议的中心增加了价值和效率。JAX在动物生产、畜牧业、评估和数据管理方面也提供了无与伦比的记录，以应对该项目的挑战。JAX KOMP2表型中心将：1)获得1250个突变株的主要单只小鼠数据，每个菌株有235种表型；2)对每个突变株的表型进行定量和定性评估，采用自动调用程序，进行统计、技术和科学审查；3)及时、高效地向KOMP2数据采集中心提供表型数据；4)开发创新方法来提高表型过程的效率和这些数据对科学界的价值。我们提出了一种双管道策略，从每个KO菌株的2个队列中收集必要的生理数据，然后进行深入的尸检和组织学检查，以完成多器官系统的评估。一个管道专门用于评估行为，神经生理学，视觉，睡眠和听力，另一个管道捕获代谢，心血管和免疫功能。我们通过增加在大规模研究中未被充分代表的表型（如睡眠），并通过整合创新和技术发展的机会，进一步简化流程并确定降低总体成本的方法，增强了管道设计的价值。我们已经组建了一个领域专家小组，为所有数据提供常规质量保证，并参与对每个KO菌株的综合评估。这项工作将促进作为人类疾病模型的KO菌株的鉴定，并为消除单个基因的功能后果提供见解。

DESCRIPTION (provided by applicant): The Jackson Laboratory (JAX) is well positioned to fully participate as a member of the KOMP2 Research Network and support its objectives to build a global resource for understanding mammalian gene function. JAX is a leading center for mouse genetics and the development of mouse models of human disease. Drawing from deep cumulative knowledge and the unique spectrum of expertise of Jackson Laboratory scientists, we have assembled the necessary leadership and created a blueprint for a cost-effective JAX KOMP2 Phenotyping Center that will produce high quality functional assessments of KOMP strains. Demonstrated experience and proven success in numerous previously funded high throughput phenotyping programs at JAX adds value and efficiency to our proposed Center. JAX also offers an unparalleled track record for animal production, husbandry, evaluation and data management required to meet the challenges of this project. The JAX KOMP2 Phenotyping Center will: 1) obtain primary, per-mouse data for 1,250 mutant strains across 235 phenotypes per strain; 2) provide quantitative and qualitative assessment of phenotypes for each mutant strain, using automated calling procedures, statistical, technical and scientific review; 3) deliver phenotypic data to the KOMP2 Data Collection Center in a timely and efficient manner; and 4) develop innovative approaches to increase the efficiency of phenotyping processes and the value of these data to the scientific community. We present a dual-pipeline strategy to collect essential physiological data from 2 cohorts of each KO strain, followed by in-depth necropsy and histology to complete the assessment of multiple organ systems. One pipeline is devoted to evaluation of behavior, neurophysiology, vision, sleep and hearing, and a second pipeline captures metabolic, cardiovascular and immune function. We have augmented the value of the pipeline design by adding phenotypes underrepresented in large-scale efforts, such as sleep, and by integrating opportunities for innovation and technology development to further streamline the process and identify ways to reduce overall costs. We have assembled a panel of Domain Experts to provide routine quality assurance of all data and participate in comprehensive assessments for each KO strain. This effort will promote the identification of KO strains as models for human disease and provide insight into functional consequences of eliminating a single gene.