KOMP Phase II Mouse Phenotyping

KOMP II 期小鼠表型分析

• 批准号: 8333313
• 负责人: KC KENT LLOYD
• 金额: $ 264.2万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-16 至 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8333313
• 关键词: Adult; Affect; Arrhythmia; Back; Behavior; Biological Assay; Biology; Brain; California; Cardiac; Cardiovascular system; Chemicals; Chemistry; Clinical Chemistry; Code; Communities; Contractor; DNA Sequence; Data; Data Set; Development; Disease; Electrophysiology (science); Embryo; Ethylnitrosourea; Europe; Funding; Future; Gene Expression; Gene Expression Profile; Genes; Genetic; Genetic Programming; Genetic Variation; Genome; Goals; Hematology; Hematopoiesis; Heterozygote; Histopathology; Human; Image; Institutes; Institution; International; Internet; Investments; Knockout Mice; LacZ Genes; Magnetic Resonance Imaging; Metabolic; Methodology; Methods; MicroRNAs; Molecular; Mus; Mutagenesis; Mutant Strains Mice; Mutation; Neonatal; Neurobiology; Participant; Pathology; Pediatric Hospitals; Phase; Phenotype; Placenta; Procedures; Production; Proteins; Provider; Recommendation; Research; Research Infrastructure; Research Institute; Research Personnel; Resources; Respiratory physiology; Series; Serum; Services; Site; Staging; Standardization; Technology; Testing; Trust; United States National Institutes of Health; Work; airway hyperresponsiveness; base; cost; disorder risk; experience; gene function; imaging modality; immune function; innovation; mammalian genome; mature animal; member; metabolomics; molecular phenotype; mutant; neonate; new technology; novel; programs; repository; technology development; tool

DESCRIPTION (provided by applicant): The objective of this K0MP2 project is to provide comprehensive phenotyping of 200 KOMP mutant mouse lines each year for five years. This will provide significant new information regarding gene function, especially for un-annotated genes, to the research community and will accelerate our understanding of the genetic basis of disease. This goal will be achieved by a consortium having a significant track-record in mutant mouse production, phenotyping, technical innovation and working together on collaborative projects. The UCD-TCP-CHORI consortium consists of the Mouse Biology Program at U. California Davis (UCD), the Toronto Center for Phenogenomics (TCP), and Children's Hospital of Oakland Research Institution (CHORI). In this application, we propose phenotyping 200 homozygous K0MP2 mutant lines each year: 150 adult mutant lines will be phenotyped at the UCD - CHORI site using a single pipeline approach and integrating molecular phenotyping into the assessment; and 50 sub-viable lines will be phenotyped at TCP along with adult phenotyping of heterozygotes for a subset of the embryonic lethal lines. In addition, TCP will assess homozygous mutant adult lung function using a well established challenge test in a subset of the adult-viable mutant lines. Methods, procedures-and best practices for adult phenotypes shared among the UCD-TCP-CHORI consortium members will be harmonized. The plan integrates well with the recommendations of the International Mouse Phenotyping Consortium, but we have recommended changes that will save significant resources, and provide rich novel datasets. Innovations include: A) a single pipeline approach for the adult-viable lines; B) intensive and detailed embryonic lethal phenotyping that incorporates several imaging modalities; C); targeted sub-viable mutant phenotyping; and D) intelligent transcriptome analyses in homozygous adult. Also, we propose an intensive technology development program to apply the revolutions in DNA sequencing technology to refine, tailor and optimize RNAseq for transcriptome analyses and to explore other molecular phenotypes such as micro RNA profiling, and metabolomics for future incorporation into the phenotype screens.

描述（由申请人提供）：该 K0MP2 项目的目标是在五年内每年提供 200 个 KOMP 突变小鼠品系的全面表型分析。这将为研究界提供有关基因功能的重要新信息，尤其是未注释的基因，并将加速我们对疾病遗传基础的理解。这一目标将由一个在突变小鼠生产、表型分析、技术创新和合作项目方面拥有重要记录的联盟来实现。 UCD-TCP-CHORI 联盟由加州大学戴维斯分校小鼠生物学项目 (UCD)、多伦多表型组学中心 (TCP) 和奥克兰儿童医院研究所 (CHORI) 组成。在此应用中，我们建议每年对 200 个纯合 K0MP2 突变系进行表型分析：将使用单一管道方法在 UCD - CHORI 站点对 150 个成年突变系进行表型分析，并将分子表型分析整合到评估中； 50 个亚存活系将在 TCP 上进行表型分析，同时对胚胎致死系子集的杂合子的成年表型进行分析。此外，TCP 将使用成熟的挑战测试来评估纯合突变体成年肺功能。 UCD-TCP-CHORI 联盟成员之间共享的成人表型的方法、程序和最佳实践将得到协调。该计划与国际小鼠表型联盟的建议很好地结合在一起，但我们建议进行更改，这将节省大量资源，并提供丰富的新颖数据集。创新包括：A）针对成人可行品系的单一管道方法； B) 结合多种成像方式的密集且详细的胚胎致死表型分析； C）；靶向亚活突变体表型分析； D) 纯合成人的智能转录组分析。此外，我们还提出了一项密集的技术开发计划，以应用 DNA 测序技术的革命来细化、定制和优化用于转录组分析的 RNAseq，并探索其他分子表型，例如 micro RNA 分析和代谢组学，以便将来纳入表型筛选。