The researchers chose to create a mouse atlas, partly because mouse tissue is smaller and much easier to access than human tissue, but also because mice are a common lab animal and can be easily manipulated genetically.
Barres at Stanford, for example, studies the neural cells that form myelin, an insulating sheath for neurons that degenerates in multiple sclerosis (MS). “We found using the atlas that some genes involved in myelin formation are only expressed in certain parts of the myelin,” says Barres. “It’s been known that MS affects some regions of the brain and not others, so these findings suggest a new hypothesis for what’s going on.” He plans to compare gene expression patterns to gene expression in a mouse that has been genetically engineered to have a disease similar to multiple sclerosis.
At Caltech, Anderson studies the amygdala, a brain area that plays a role in fear and anxiety and has also been implicated in autism, a developmental disorder characterized by cognitive and social problems. He says the amygdala is made up of several different parts that are difficult to distinguish with a microscope. Anderson says the brain atlas shows that these subregions have distinct patterns of gene expression. Now he and other researchers can look at the development of these specific areas, to see how they might be altered in autism.
Researchers at the Allen Institute are just beginning to mine the massive database of information they’ve generated. Nonetheless, they’ve already uncovered some interesting findings. “Approximately 80 percent of the genes in the genome are expressed in the brain, which is greater than the previous estimates of 60-70 percent,” says Kelly Overly, research alliance manager at the Allen Institute. “The genome is much more represented in the brain than we thought.”
She adds that the finding has implications for drug development: if scientists are developing new drugs that target gene products found in both the brain and body, they can try to avoid targeting areas not involved in the disease.
The institute is now planning a new project focusing on the neocortex, the brain area responsible for higher thought. They will use data from the mouse atlas, as well as from human tissue samples, to try to better understand the phenomenon of complex thought. Researchers are also collaborating with other institutions to study autism, epilepsy, and ALS. Comparing gene-expression patterns in the brain atlas with that of animal models of these diseases can shed light on exactly what’s gone awry.
“That information can be a huge help in focusing research efforts to understand diseases, as well as hopefully developing new and better therapeutics,” says the Allen Institute’s Overly.