Diversity Outbred Mice May Predict Potential Human Responses to Chemical Exposures
NTP researchers found that a genetically diverse mouse model may better predict the potential range of response to chemical exposures observed among humans compared to traditional mouse models. Each Diversity Outbred mouse is genetically unique, and the extent of genetic variability among these mice is similar to the genetic variation seen among humans.
In this research project, the mice were exposed to benzene, and, like humans, each Diversity Outbred mouse responded to the effects of benzene exposure differently. Benzene is a common air pollutant and human carcinogen found in crude oil, gasoline, and cigarette smoke, and naturally produced by wildfires and volcanoes. Scientists assessed the biological response of the mice by measuring the frequency of micronucleated red blood cells, a blood-borne marker of chromosomal damage, which is a hallmark of benzene exposure.
Some mice demonstrated sensitivity to benzene exposure, while others showed no response. There was about a five-fold difference between lowest to highest response. Because the researchers knew the genetic makeup of each mouse, they could pinpoint the genomic regions involved in susceptibility or resistance to the chemical exposure, and then look for related genetic regions in human chromosomes.
These results may lead to further research to better understand genetically regulated responses to toxicity in humans, as well as mechanisms of susceptibility and resistance to environmental exposures as they relate to disease. The paper describing these findings was published in Environmental Health Perspectives in FY 2015.
Jef French, Ph.D., who is now retired, devoted several years to studying in vivo animal models to explore individual variability in toxicity response. (Photo courtesy of Steve McCaw)