Researchers Map Genetic Differences in Mouse and Human Immune Systems
Early research and trials often experiment on mouse models despite the fact that mice and humans might differ more than the researchers would like. Several findings that are promising in lab rats fail to have any effects on humans. Despite this fact, researchers have to start somewhere and the lab rats might be the closest and most accessible animals to experiment on. According to a study by a research team from Harvard Medical School, the Broad and Stanford University, they found that the differences in the gene expressions of mouse and human immune systems help explain the discrepancies between the success rates of certain experiments between the two.
The research team was headed by Tal Shay, a postdoctoral associate in Aviv Regev's lab at the Broad Institute of Harvard and MIT. They looked into how genes get expressed and represented in both the mouse and the human profiles based off of immune cell types. The team looked at gene expressions in 80 human and 137 mouse samples and found numerous genes in seven immune cell types that were different between the two groups. The process of comparing human gene expression to mouse gene expression was complicated and lengthy. The researchers had to find the exact corresponding type in both animals before they could conclude whether or not the human and mice's immune cell type were similar or dissimilar.
"We wanted to pinpoint where immune system genes and gene expression are different and where you should be very suspicious if something is found in mouse and likely to be translated to human," Shay stated. "We thought we might be able to map those places where the comparison is less robust, but we had a very hard time pinpointing convincing differences."
The researchers found that certain genes found in mice could not be directly compared to human genes at all while other genes in mice could be compared to a set of genes in humans. After determining which mouse genes were linked to human genes, the researchers also looked into other factors, such as infections and how they activate certain areas of the genes in both groups. The study was able to find areas in both the humans and mice that might have more similarities than other areas, which suggests the research in those areas in mice could be beneficial for humans.
"What we assume most people will be interested in knowing is, if they are working on gene X, whether gene X has the same expression pattern in human and mouse immune systems. Most lineages have the same expression signature but some genes behave differently and we think it's important for why some things work in mice but not humans and the other way around," Shay added.
Although the study did not find clear and distinctive similarities between the gene expressions of humans and mice, it did provide a better understanding of why certain studies done in mice generate positive results but cannot be translated to humans.
The study was published in PNAS.