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Mice Get Freakishly Large Brains Thanks to Human DNA

Where is Pinky, because we got the Brain.

by Becky Ferreira
Feb 19 2015, 9:25pm

​A mouse embryo with some premium HARE5 enhancers. Image: Silver lab, Duke University

Super-intelligent lab mice are a common trope of science fiction, ranging from the heartrending Flowers for Algernon tale to the beloved Pinky and the Brain TV series. But today, scientists announced that they have boosted brain size in mice for real, using human DNA as a catalyst.

The study's authors, based out of Duke University, successfully produced an excessively brainy mouse embryo by isolating a key genetic sequence involved in human brain growth. Their results were published today in Current Biology.

"Many others have tried this and failed," co-author Gregory Wray said in a statement. "We've known other people who have looked at genes involved in brain size evolution, tested them out, and done the same kinds of experiments we've done and come up dry."

The Duke team tracked down this elusive sequence by comparing the genomes of humans and chimpanzees. They further narrowed the focus to include only sequences that were significantly different between the species, which revealed 106 "enhancer" sequences—meaning that these short bits of DNA interact with neighboring genes and control their activity.

From there the team isolated the right enhancer by identifying which sequences were located closest to proteins involved in early brain tissue development. They zeroed in a sequence called HARE5, and introduced both the human and chimpanzee versions of the strand into mouse embryos.

Though the two primates' HARE5 sequences differ by only 16 letters, they delivered dramatically different results. The mouse embryos with the human enhancer grew brains that were 12 percent bigger than those with chimp enhancers.

In a stroke of artistic genius, the team also built in a "reporter" gene, instructed to stain the mouse's brain blue whenever the enhancer modified gene expression. Behold, a delightfully creepy tale written on a neural canvas.

Brainiac mouse. Image: Silver lab, Duke University

The Duke study has obvious implications for our understanding of the human cognitive abilities, as well as their relative standing with other animals. But it could also have huge repercussions for treating neurological diseases. Chimps, for instance, don't suffer from ​Alzheimer's disease, and figuring out the genetic reason why might lead to better treatments for the humans who do.

"I think we've just scratched the surface, in terms of what we can gain from this sort of study," said study co-author Debra Silver. "There are some other really compelling candidates that we found that may also lead us to a better understanding of the uniqueness of the human brain."