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12:00 AM
Sep 24, 2015
 |  BC Innovations  |  Tools & Techniques

Knocks heard 'round the world

Consortium to knock out every gene in mice could be model for collaboration

While researchers typically create knockout mice to ask specific questions about a gene, the International Mouse Phenotyping Consortium (IMPC) wants to get a full picture of every gene's function by creating knockout mice for the entire genome. At its annual meeting, the consortium announced it is more than halfway toward the first goal of phenotyping 5,000 uncharacterized genes, and its leaders believe the cooperative system they have developed could be a blueprint for emerging consortia like the Precision Medicine Initiative.

Although it's taken about 10 years to reach this point, Steve Brown, chair of the IMPC international steering committee and director of the Medical Research Council (MRC) Harwell mouse phenotyping center, told BioCentury the group is on track to complete the first 5,000 genes by next year, and the full 21,000 that make up the genome by 2021. That progress is due in part to the growing number of groups that are signing on to join the consortium, but also because of technical advances in gene editing that make the process of generating knockout mice faster and easier.

Last week, the IMPC brought together representatives in Seoul, South Korea, from its 18 worldwide centers to review the progress of its program.

The consortium's overarching strategy is to knock out close homologs of human genes one by one in mice, and document how the knockout mice differ from wild-type mice across hundreds of physiological parameters, based on metabolic, hematologic, cardiac and neuromuscular readouts.

The hope is that the effort will identify a vast array of new disease models, therapeutic targets and diagnostic markers.

"Having knowledge of what those genes do as a result of our project is going to dramatically accelerate the interpretation of those variants in people, and eventually lead to better diagnoses and hopefully to targeted therapies," said Kent Lloyd, director of the mouse biology program at the University of California Davis and a member of the IMPC steering committee.

Although using mouse knockouts to investigate how a gene functions in a particular pathway or pathology has been common practice for over 20 years, a growing trend has emerged toward screening for gene function in a more unbiased way. Several collaborations set up to do this in the U.S. and Europe combined their efforts in 2011 under the mantle of the IMPC. (See Figure: International Relations)

The IMPC is now supported by five North American and European funding agencies, and includes 18 centers across four continents.

"For many years, a lot of research groups were making mouse knockouts and examining them for interesting phenotypes," said...

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