The Knockout Mice Project

The most commonly observed abnormalities included slowed growth and embryonic development. They also saw many abnormalities in cardiovascular development, malformations of the head and face, and defects in limb development.

As evidence to suggest the findings are relevant to understanding human disease, the researchers showed that loss-of-function mutations for those essential mouse genes are rarely found in the corresponding genes of living people. The finding suggests those genes are also essential to human life and health and could be good places to look for answers to miscarriages, stillbirths, or unexplained genetic conditions in people.

There were some surprises, too. Despite the fact that researchers in the consortium all conducted their studies according to standardized protocols, embryonic mice carrying exactly the same set of genes didn’t always share the same physical features or experience the same life or death outcomes. The findings suggest that in addition to genes and environmental factors, other seemingly random events during development can also play an important role.

The work is ongoing. In fact, the consortium already has data on hundreds more knockout mice available, just waiting to be analyzed. All of the data is being openly provided in real time to investigators around the world to explore and expand on as needed. The consortium is also making the knockout mice themselves available to enable other researchers with particular interests to study them in even greater detail.

It goes to show the remarkable progress to be made in biomedicine when researchers around the world rally as a team around a common approach to achieve a common goal. That’s a great take-home message.

References:

[1] Knockout Mouse Project (KOMP) Repository (University of California, Davis and Children’s Hospital Oakland Research Institute)

[2] High-throughput discovery of novel developmental phenotypes. Dickinson ME, Flenniken AM, Ji X, Teboul L, Wong MD, White JK, Meehan TF, Weninger WJ, Westerberg H, Adissu H, Baker CN, Bower L, Brown JM, Caddle LB, Chiani F, Clary D, Cleak J, Daly MJ, Denegre JM, Doe B, Dolan ME, Edie SM, Fuchs H, Gailus-Durner V, Galli A, Gambadoro A, Gallegos J, Guo S, Horner NR, Hsu CW, Johnson SJ, Kalaga S, Keith LC, Lanoue L, Lawson TN, Lek M, Mark M, Marschall S, Mason J, McElwee ML, Newbigging S, Nutter LM, Peterson KA, Ramirez-Solis R,…

International Mouse Phenotyping Consortium

International Knockout Mouse Consortium

Knockout Mice Fact Sheet (National Human Genome Research Institute/NIH)

Steve Murray (The Jackson Laboratory, Bar Harbor, ME)

Mary Dickinson (Baylor College of Medicine, Houston)

The Centre for Phenogenomics (Toronto, Canada)

Medical Research Council Harwell (Oxfordshire, U.K.)

Maja Bucan (University of Pennsylvania, Philadelphia)

NIH Support: National Human Genome Research Institute; Common Fund