The Jackson Laboratory KOMP2 Phenotyping Center

描述（由申请方提供）：杰克逊实验室（JAX）处于有利地位，可以作为KOMP 2研究网络的成员全面参与，并支持其建立了解哺乳动物基因功能的全球资源的目标。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层，并为具有成本效益的JAX KOMP 2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。在JAX的许多先前资助的高通量表型分析项目中展示的经验和证明的成功为我们拟议的中心增加了价值和效率。JAX还为满足该项目的挑战所需的动物生产，畜牧业，评估和数据管理提供了无与伦比的跟踪记录。JAX KOMP 2表型分析中心将：1）获得1，250个突变品系的每只小鼠的主要数据，每个品系有235种表型; 2）使用自动调用程序、统计、技术和科学审查，对每个突变品系的表型进行定量和定性评估; 3）及时有效地向KOMP 2数据收集中心提供表型数据;以及4）开发创新方法以提高表型分析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，然后进行深入尸检和组织学检查，以完成多器官系统的评估。一条管道专门用于评估行为，神经生理学，视觉，睡眠和听力，第二条管道捕获代谢，心血管和免疫功能。我们通过增加在大规模工作中未被充分代表的表型（如睡眠），并通过整合创新和技术开发的机会来进一步简化流程并确定降低总体成本的方法，从而增强了管道设计的价值。我们组建了一个领域专家小组，为所有数据提供常规质量保证，并参与对每种KO菌株的全面评估。这一努力将促进KO菌株作为人类疾病模型的鉴定，并提供消除单个基因的功能后果的见解。

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.