The long-term goal of the International Knockout Mouse Consortium (IKMC) is to develop a resource of targeted mutations in mice for every protein-coding gene in the mammalian genome that the research community can use to elucidate gene function in human biology and disease. Within this framework, the objective of the first phase of the KOMP^ program is to generate 2,500 well-characterized knockout (KO) lines over five years. The program will establish a system of interactive centers in three functional areas: production and preliminary phenotyping of KO strains;broad-based phenotyping;and informatics and database support for the program. This application describes our plan to establish a KO Mouse Production and Cryopreservation Center at The Jackson Laboratory (JAX). JAX has the exceptional expertise, experience, and resources to efficiently and cost-effectively carry out the Center functions on the large scale required. The Center will leverage multiple JAX resources including the JAX Repository, a major community mouse resource program;Reproductive Sciences, a world leader in strain cryopreservation and innovative research;and outstanding data-management systems and expertise. To meet the Center objectives we will: 1) Generate up to 2,500 KO mouse lines from IKMC ES cells;2) Test and analyze KO mice for viability and fertility, and examine LacZ expression patterns of each allele;3) Breed, cryopreserve, and distribute animals and/or germplasm to KOMP^ Phenotyping Centers;and 4) Reduce the cost of providing mice and germplasm to the Phenotyping Centers through the use of innovative technologies. We will use existing, extensible mouse data-management and laboratory information management systems (LIMS) at JAX to track all data and communicate it to the KOMP^ Data Coordination Center Database (DCCDB). Together with the Phenotyping Centers and the DCCDB, this project promises to deliver a critical resource to the scientific community.
The mouse is a critical animal model for understanding gene function and developing accurate models of human disease. This proposal aims to generate up to 2500 new mutant mouse lines as part of the KOMP Program, providing a valuable resource to the scientific community. The Jackson Laboratory has the outstanding expertise, experience, and resources to efficiently and cost-effectively meet this goal.
|Meehan, Terrence F; Conte, Nathalie; West, David B et al. (2017) Disease model discovery from 3,328 gene knockouts by The International Mouse Phenotyping Consortium. Nat Genet 49:1231-1238|
|Bowl, Michael R; Simon, Michelle M; Ingham, Neil J et al. (2017) A large scale hearing loss screen reveals an extensive unexplored genetic landscape for auditory dysfunction. Nat Commun 8:886|
|Snyder, Elizabeth M; McCarty, Christopher; Mehalow, Adrienne et al. (2017) APOBEC1 complementation factor (A1CF) is dispensable for C-to-U RNA editing in vivo. RNA 23:457-465|
|Liu, Xiaoqin; Yagi, Hisato; Saeed, Shazina et al. (2017) The complex genetics of hypoplastic left heart syndrome. Nat Genet 49:1152-1159|
|Karp, Natasha A; Mason, Jeremy; Beaudet, Arthur L et al. (2017) Prevalence of sexual dimorphism in mammalian phenotypic traits. Nat Commun 8:15475|
|Shaheen, Ranad; Anazi, Shams; Ben-Omran, Tawfeg et al. (2016) Mutations in SMG9, Encoding an Essential Component of Nonsense-Mediated Decay Machinery, Cause a Multiple Congenital Anomaly Syndrome in Humans and Mice. Am J Hum Genet 98:643-52|
|Dickinson, Mary E; Flenniken, Ann M; Ji, Xiao et al. (2016) High-throughput discovery of novel developmental phenotypes. Nature 537:508-514|
|Leduc, Magalie S; Niu, Zhiyv; Bi, Weimin et al. (2016) CRIPT exonic deletion and a novel missense mutation in a female with short stature, dysmorphic features, microcephaly, and pigmentary abnormalities. Am J Med Genet A 170:2206-11|
|Lloyd, K C Kent; Meehan, Terry; Beaudet, Arthur et al. (2015) Precision medicine: Look to the mice. Science 349:390|
|Zhao, Lihong; Spassieva, Stefka; Gable, Kenneth et al. (2015) Elevation of 20-carbon long chain bases due to a mutation in serine palmitoyltransferase small subunit b results in neurodegeneration. Proc Natl Acad Sci U S A 112:12962-7|
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