Researchers investigating host responses to Ebola have long faced a significant disadvantage: the virus kills conventional lab mice, but does not produce the hemorrhagic fever or other classical symptoms that occur in humans. The lack of a mouse disease model has hampered studies on the pathology and immunology of Ebola infections, as well as the development of treatments.
A team led by Angela Rasmussen and Michael Katzeof the University of Washington and Atsushi Okumura of the US National Institutes of Health (NIH) Rocky Mountain Laboratories has tested responses to Ebola in 47 genetically diverse mouse lines, demonstrating considerable variability in disease outcomes. The results, reported today (October 30) in Science, lay the groundwork for analyses of genetic differences in susceptibility to Ebola.
The study “confirms what a lot of people are starting to appreciate,” said David Threadgill, a geneticist at Texas A&M University who was not involved in the research. “Looking at single mouse strains, which is historically what’s done, completely misses the vast majority of biology,” he added.
Threadgill was among the scientists who first proposed creating the mouse collection used in the study, called the Collaborative Cross (CC). The CC consists of hundreds of genotypically distinct mouse lines bred from eight original strains—five lab strains and three inbred strains originating from wild populations. While lab strains are largely derived from a single subspecies, Mus musculus domesticus, CC mice represent much of the genetic variation present in three subspecies, and have almost four times as many single-nucleotide polymorphisms as conventional lab strains.