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Building a better mouse model

  • Principal Investigator: Kathleen Millen, Associate Professor of Human Genetics; Committee on Genetics; and Committee on Neurobiology at the University of Chicago
  • Amount: $500,000 (year one); $499,998 (year two)
  • Source: National Institutes of Health ARRA Funding
  • Goal: Develop a fast, inexpensive way to generate mouse models to study human genetic diseases


The Human Genome Project has allowed scientists to readily identify regions of the genome where diseases reside, but each region includes many genes. Trying to determine specifically which of those genes have something to do with a particular disease is expensive and time consuming, creating huge bottlenecks in many fields of study.

Millen thinks she has found a way to fix this problem. Researchers use mouse models to study human disease because mice are easy to work with and closely related to humans, genetically speaking. To use a mouse as a model, researchers genetically engineer a mouse by turning off one or more of its genes, resulting in what is called a knockout mouse. Next they try to determine the function of the gene(s) that was (were) turned off by observing the difference between a normal mouse and the knockout. If the knockout manifests signs of the disease being studied, the gene that was turned off is probably involved. This process was developed in the 1980s and won its inventors the Nobel Prize for medicine in 1989.

The problem with this process, however, is that each knockout mouse takes about one and one-half years to engineer and costs $50,000 in reagents alone, limiting the number of mice that can be generated. Millen’s new technique would take only 2 months and cost about $2,000, allowing the researchers to quickly and inexpensively generate mice to test the function of a large number of disease-candidate genes.

"If this works, it will revolutionize disease-candidate gene analysis," Millen said. "We will be able to identify disease genes quicker and therefore find cures to human diseases faster."

"We plan to make the technology available for free to academic researchers," she added. “It would be too important to hold onto."

Millen’s novel strategy combines recent advances in breeding mice, evaluating the diseases of genetically altered mice, and applying RNA interference, which blocks the expression of select genes. Parts of the technique could be patented.

Millen has been mulling ideas about combining these techniques in a novel way for more than two years. "I don't think it would have been funded by traditional grant mechanisms," she said. "Funding was really only possible because part of the stimulus package was focused on funding risky, high impact projects," she said.

"The stimulus package has been a boon to science," she added. "Nevertheless, it's a stopgap measure. There needs to be a stronger, more long-term commitment to science funding."

by Greg Borzo

This award is funded under the American Recovery and Reinvestment Act of 2009, NIH Award number: 1RC1HD063610-01. For more information on NIH’s Recovery Act projects, visit

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