Database of Gene Activity in Mice Developed

A comprehensive database of gene activity in mice across ten disease models has been developed by scientists at the Francis Crick Institute. It provides a full picture of the immune response to different pathogens, according to the team.

The data, published yesterday in Nature Communications and available through an online app, shows the activity of every mouse gene—more than 45,000 genes—in the blood of mice with ten different diseases. For the six diseases that involve the lung, samples from lung were also examined.

Previously, researchers would have to create, infect, cull, obtain samples from mice and extract and sequence the RNA to study genes that they are interested in. Using the app that the lab created for this study, researchers will be able to check the activity of any gene across a range of diseases without needing their own mice. This could prevent thousands of mice being used in individual experiments.

The research team, led by Crick group leader Anne O'Garra, used RNA-seq, to measure gene activity across the different diseases. "Gene activity can show us how the body responds to infections and allergens," explains O’Garra. "There are thousands of genes involved in any immune response, so Akul Singhania, a Bioinformatics Postdoc, in our lab used advanced bioinformatics approaches to cluster the genes into modules. These modules represent clusters of genes that are co-regulated and can often be annotated to determine their function and known physiological roles. For example, of 38 lung modules there is a module associated with allergy, and seen only in the allergy model, containing over 100 genes and another module associated with T cells containing over 200 genes."

"By sequencing both lung tissue and blood, we can also see how the immune response in the blood reflects the local response in the lung, and vice versa. This will help us to understand what we can learn from genetic signatures in the blood, since for most diseases doctors can't realistically get lung samples from patients."

Using the app, researchers can look up gene activity in the lungs and blood of mice infected with a range of pathogens: the parasite Toxoplasma gondii, influenza virus and Respiratory Syncytial Virus (RSV), the bacterium Burkholderia pseudomallei, the fungus Candida albicans, or the allergen, house dust mite. They can also see gene activity in the blood of mice with listeria, murine cytomegalovirus, the malaria parasite Plasmodium chabaudi chabaudi, or a chronic Burkholderia pseudomallei infection.

Image by Karsten Paulick from Pixabay