Background

One of the most important tools at our scientific disposal in understanding mammalian gene function is the laboratory mouse. The scientific community has taken advantage of its fundamental similarity to humans at the genetic level (>95% at the gene level), its similar physiology and anatomy, its relative low cost compared to other mammals, and nearly 100 years of genetic study.

There is an extensive toolkit for the manipulation of the mouse genome and the generation of new disease models. After completing the mouse genome sequence, an international consortium was developed, the International Knock-out Mouse Consortium (IKMC) to systematically generate mutant ES cells for every gene in the mouse genome (20,000 plus genes).

The IMPC builds on the efforts of IKMC to produce knockout mice and carry out high-throughput phenotyping of each line in order to determine the function of every gene in the mouse genome. These mice will be preserved in repositories and made available to the scientific community representing a valuable resource for basic scientific research as well as generating new models for human diseases.

The approaches that are being developed build on the efforts of a number of pilot programs around the world such as the EUMODIC program and the MGP program. The European EUMODIC consortium generated and phenotyped 500 mouse strains in a high-throughput fashion. This was completed early in 2012.

From 2012, the IMPC took over the task to generate knockout mice and phenotype the remainder of the 20,000 plus genes in a worldwide coordinated initiative.

IMPC Goals

• Establish a world-wide consortium of mouse centres with capacity and expertise for large-scale primary phenotyping.
• Establish a world-wide consortium of mouse production centres to generate germ line transmission of targeted knockout mutations in embryonic stem cells for all known and predicted mouse genes.
• Test each mutant mouse line (4,000 mouse lines in the first 5 years, and ultimately up to 20,000) through a broad-based primary phenotyping pipeline in all the major adult organ systems and most areas of major human diseases. Through this activity and employing data annotation tools, systematically aim to discover and ascribe biological function to each gene, driving new ideas and underpinning future research into biological systems.
• Establish collaborative “networks” with specialist phenotyping consortia or laboratories, providing standardized secondary phenotyping that enriches the primary dataset, and end-user, project specific tertiary level phenotyping that adds value to the mammalian gene functional annotation and fosters hypothesis driven research.
• Provide a centralized data centre and portal for free, unrestricted access to primary and secondary data by the scientific community, promoting sharing of data, genotype-phenotype annotation, and the development of open-source data analysis tools.