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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.

国际小鼠表型鉴定协会（IMPC）的目标是开发一个无效等位基因资源小鼠基因组中每一个蛋白质编码基因的序列，并通过标准化的，广泛的表型分析，对每个靶基因的生物学功能进行分类。NIH资助的敲除小鼠表型分型项目（KOMP2）已经支持了无效等位基因产生和表型分型的两个先前阶段，这有助于超过一半的由IMPC制备和表征的无效等位基因系。本申请描述了我们的计划，贝勒医学院（Baylor College of Medicine）将继续作为KOMP2网站在第三阶段，经费我们建议生产，冷冻保存，和表型无效等位基因小鼠品系为600蛋白编码基因.我们已经开发了一种生物信息学方法来识别和优先考虑已知或推定的基因，人类疾病相关性，但对于无效等位基因小鼠系生产几乎没有体内功能注释。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，使用可接受的技术冷冻保存所有无效等位基因系，并将种质递送到用于社区范围分发的MMRRC存储库。这些无效等位基因系代表了黄金标准资源为科学界和未来的研究和转化研究的重要基础。我们将利用我们建立的管道对所有突变株系进行广泛的标准化成人表型分析并评估胚胎表型分析管道中的纯合致死和亚存活品系。的表型分型我们获得的数据将为哺乳动物生物学以及遗传基础提供新的基本见解人类疾病。所有等位基因和表型数据将真实的提交给数据协调中心，确保向更广泛的生物医学科学界迅速传播所有可持续发展数据。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，在社区出现新的方法时采用它们。KNOKOMP2团队拥有既定的专业知识、经验和资源，以高效和具有成本效益的方式实现拟议的第3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.