- Introduction to Clinical Research Training
- Medical Education
- United Kingdom Clinical Scholars Research Training
- Vanderbilt Hall
- Financial Aid
- Office of the Registrar
- Campus Planning and Facilities
- Ombuds Office
- Committee on Microbiological Safety
- Human Resources
- HMS Foundation Funds
- Office for Academic and Clinical Affairs
- Joint Committee on the Status of Women
- The Academy
- Global Health Research Core
- Global Clinical Scholars Research Training Program
- HMA Standing Committee on Animals
- Office of Research Compliance
- Global & Community Health
- Harvard Medical School Event Calendar
- Contact @HMS
- Office of Diversity RIA Program
- The Dean's Perspective
- Department of Pathology
- Harvard Mahoney Neuroscience Institute
- OHRA Home
- Office of Research Subject Protection
- Tools and Technology
- Alumni Association
- Cancer Biology & Therapeutics Program
- Celiac Program
- Department of Medicine
- HMS Community Values Initiative
- HMS Information Technology
- HMS TransMed Program
- Introduction to the Practice of American Medicine
- Office of Communications & External Relations
- Master of Medical Sciences In Clinical Investigation
- Office of Global Education
- Portugal Clinical Scholars Research Training Program
- Shenzhen-HMS Initiative in International Education
- South American Clinical Research Training
- test page
- Safety Quality Informatics and Leadership
- Human Resources
- Jobs @ HMS
- Dental Medicine
- Harvard University
- Contact us
Of Men, Not Mice
Existing mouse models do not appear to accurately reproduce the human genomic response to serious traumatic injury, including major burns, according to an article appearing in PNAS Early Edition.
The report from a national consortium investigating the role of inflammation in the body’s response to injury finds little correlation between the human response to burns, trauma or a bacterial toxin and that of currently used mouse models for those conditions. The authors noted that their results cannot be applied to the use of mouse models for other research purposes.
“Our findings question the validity of using mouse models to mimic inflammatory conditions in humans,” said Shaw Warren, HMS associate professor of pediatrics at Massachusetts General Hospital and a co-lead author of the report.
“An additional finding is that the whole-genome responses to these conditions in humans correlated well with each other, suggesting that treatments developed for an inflammatory disease from one cause might also work for inflammatory diseases with different causes,” Warren said.
The study is part of the Inflammation and the Host Response to Injury consortium, established in 2001 to investigate how the human body responds to injury, with particular attention to factors that set off excessive, uncontrolled inflammation.
Based at Mass General, the program includes investigators from 20 academic research centers around the country and is led by Ronald G. Tompkins, HMS Sumner M. Redstone Professor of Surgery and director of the Sumner Redstone Burn Center at Mass General. He is a co-corresponding author of the current report.
In 2011, the group reported finding that serious injuries set off a “genomic storm” in the human body, altering around 80 percent of normal gene expression patterns. The current study drew on information from that study and others conducted by the consortium to compare the human genomic response to inflammatory disease with that of mouse models.
The investigators from Mass General, the Stanford University Genome Technology Center and several other research centers combined data from four of their studies of genomic responses to systemic inflammation: two in burn or trauma patients and volunteers treated with a bacterial toxin that produces brief flu-like symptoms and two studies of the responses in mouse models of the three conditions.
While the responses among human patients were very similar, showing changes in the expression of more than 5,500 genes, there was very little correlation with the expression patterns of corresponding genes in the mouse models. Not only was the human genomic response to inflammatory injury much greater—affecting the expression of more than three times as many genes as in the models—but it also lasted longer, up to six months in humans compared with a few days at most in mice.
To confirm their findings, the investigators analyzed data from an additional 20 studies of acute inflammatory disease—10 in humans and 10 in mice—and found a similar lack of correlation between the response of human patients and the mouse models. In all the human studies, the genomic responses were very similar, despite differences in patient age, gender, type and severity of injury or illness, treatment and outcomes.
“Mice have been used in biomedical research for well over 50 years, in part because of the cost, size, convenience, ease of genetic manipulation and social acceptability. But it is often forgotten that mice appear to be much more resistant to inflammation and infection than humans,” said Warren.
“By studying and understanding the mechanisms by which mice differ from humans, we may be able to develop treatments that help make humans more resistant to damaging inflammation. We also hope that our article will start a broader discussion among scientists, research organizations, journals and granting and regulatory agencies as to the value of mouse models in different specific circumstances,” Warren said.
The study was supported by Defense Advanced Research Projects Agency grant W9111NF-10-1-0271; National Institute on Disability and Rehabilitation Research grant H133A070026; National Institute of General Medical Sciences grants 5P50GM060338, 5R01GM056687, R24GM102656 and 5U54GM062119; and National Human Genome Research Institute grant P01HG000205.
Sue McGreevey is manager for science & research communications at Mass General Public Affairs.
Adapted from a Mass General news release.