KOMP2 Annual meeting: The BCM Knockout Mouse Production and Phenotyping Project (BCM KOMP2)

KOMP2 年会：BCM 敲除小鼠生产和表型项目 (BCM KOMP2)

基本信息

批准号：
10842959
负责人：
Mary E Dickinson
金额：
$ 16.97万
依托单位：
BAYLOR COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-09-16 至 2027-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10842959
关键词：
Adopted Adult Alleles Anatomy Area Bioinformatics Biological Process Biology CRISPR/Cas technology Catalogs Clustered Regularly Interspaced Short Palindromic Repeats Code Collaborations Communities Cryopreservation Data Data Coordinating Center Defect Development Disease Embryo Ensure Essential Genes Exons Foundations Funding Future Generations Genes Genetic Germ Goals Human International Knockout Mice Machine Learning Mediating Medicine Methodology Mus Mutant Strains Mice Pathway interactions Phase Phenotype Procedures Production Program Development Proteins Quality Control Research Research Personnel Resources Role Site Standardization Techniques Technology Testing Time United States National Institutes of Health Work X-Ray Computed Tomography base behavior test college cost effective data quality design experience gene function genome editing human disease improved in vivo informatics infrastructure insight large scale production meetings microCT mouse genome mutant novel novel strategies phenotypic data preclinical study repository research study technology development tool translational study

项目摘要

The goal of the International Mouse Phenotyping Consortium (IMPC) is to develop a resource of null allele lines for every protein-coding gene in the mouse genome and, through standardized, broad-based phenotyping, catalog the biological function of each targeted gene. The NIH-funded Knockout Mouse Phenotyping Project (KOMP2) has supported two previous phases of null allele production and phenotyping, contributing to more than half of the null allele lines made and characterized by the IMPC. This application describes our plan for Baylor College of Medicine (BCM) to continue as a KOMP2 site during a third phase of funding. We propose to produce, cryopreserve, and phenotype null allele mouse lines for 600 protein coding genes. We have developed a bioinformatics approach to identify and prioritize genes with known or putative human disease associations but little-to-no in vivo functional annotation for null allele mouse line production. We will generate and validate null alleles using established CRISPR genome editing approaches and quality control procedures, cryopreserve all null allele lines using accepted techniques, and deliver germplasm to the MMRRC repositories for communitywide distribution. These null allele lines represent a gold standard resource for the scientific community and an important foundation for future research and translational studies. We will utilize our established pipelines to perform broad-based, standardized adult phenotyping on all mutant lines and assess homozygous lethal and subviable lines in an embryonic phenotyping pipeline. The phenotyping data we generate will provide fundamental new insights into mammalian biology as well as the genetic bases of human disease. All allele and phenotype data will be submitted in real time to the Data Coordination Center, ensuring the rapid dissemination of all BCM data to the wider biomedical scientific community. We will continue our production and phenotyping technology development programs, developing our own new approaches and adopting new methodologies from the community as they arise. The BCM KOMP2 team has the established expertise, experience, and resources to meet the proposed phase 3 goals in an efficient and cost-effective manner.

国际小鼠表型联盟 (IMPC) 的目标是开发无效等位基因的资源小鼠基因组中每个蛋白质编码基因的系，并通过标准化、基础广泛表型分析，对每个目标基因的生物学功能进行分类。 NIH 资助的基因敲除小鼠表型项目 (KOMP2) 支持无效等位基因产生和表型分析的前两个阶段，占 IMPC 制作和表征的无效等位基因系的一半以上。这个应用程序描述了我们的贝勒医学院 (BCM) 在第三阶段继续作为 KOMP2 站点的计划资金。我们建议生产、冷冻保存 600 个蛋白质编码的无效等位基因小鼠品系并进行表型分析基因。我们开发了一种生物信息学方法来识别已知或推定的基因并对其进行优先排序人类疾病关联，但几乎没有对无效等位基因小鼠系生产的体内功能注释。我们将使用已建立的 CRISPR 基因组编辑方法和质量来生成和验证无效等位基因控制程序，使用公认的技术冷冻保存所有无效等位基因系，并将种质传递到用于社区范围内分发的 MMRRC 存储库。这些无效等位基因系代表黄金标准资源对于科学界来说，也是未来研究和转化研究的重要基础。我们将利用我们已建立的管道对所有突变株系进行基础广泛、标准化的成体表型分析并评估胚胎表型分析管道中的纯合致死系和亚存活系。表型分析我们生成的数据将为哺乳动物生物学以及遗传基础提供基本的新见解人类疾病。所有等位基因和表型数据将实时提交至数据协调中心，确保所有 BCM 数据快速传播到更广泛的生物医学科学界。我们将继续我们的生产和表型技术开发计划，开发我们自己的新方法和在社区出现新方法时采用它们。 BCM KOMP2 团队已成立专业知识、经验和资源，以高效且具有成本效益的方式实现拟议的第三阶段目标方式。

项目成果

期刊论文数量（9）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Vertical transmission of a large calvarial ossification defect due to heterozygous variants of ALX4 and TWIST1.

ALX4 和 TWIST1 杂合变异导致大颅骨骨化缺损的垂直传播。

DOI：
10.1002/ajmg.a.62036
发表时间：
2021
期刊：
American journal of medical genetics. Part A
影响因子：
0
作者：
Walters,MichelleE;Lacassie,Yves;Azamian,Mahshid;Franciskovich,Rachel;Zapata,Gladys;Hernandez,PatriciaP;Liu,Pengfei;Campbell,IanM;Bostwick,BretL;Lalani,SeemaR
通讯作者：
Lalani,SeemaR

A rare description of pure partial trisomy of 16q12.2q24.3 and review of the literature.

DOI：
10.1002/ajmg.a.62368
发表时间：
2021-10
期刊：
American journal of medical genetics. Part A
影响因子：
0
作者：
通讯作者：

Application of long single-stranded DNA donors in genome editing: generation and validation of mouse mutants.

DOI：
10.1186/s12915-018-0530-7
发表时间：
2018-06-21
期刊：
BMC biology
影响因子：
5.4
作者：
Codner GF;Mianné J;Caulder A;Loeffler J;Fell R;King R;Allan AJ;Mackenzie M;Pike FJ;McCabe CV;Christou S;Joynson S;Hutchison M;Stewart ME;Kumar S;Simon MM;Agius L;Anstee QM;Volynski KE;Kullmann DM;Wells S;Teboul L
通讯作者：
Teboul L

DOI：
10.1002/ajmg.a.62699
发表时间：
2022-06
期刊：
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
影响因子：
2
作者：
Lay, Erica;Azamian, Mahshid S.;Denfield, Susan W.;Dreyer, William;Spinner, Joseph A.;Kearney, Debra;Zhang, Lilei;Worley, Kim C.;Bi, Weimin;Lalani, Seema R.
通讯作者：
Lalani, Seema R.

High Resolution Imaging of Mouse Embryos and Neonates with X-Ray Micro-Computed Tomography.