Scientists Created Mice With Half-Human Brains. The Hybrid Animals Could Revolutionize Our Understanding of Neurological Disorders

Our brains and their associated diseases are notoriously hard to study. So, researchers developed an animal model with a cortex—the brain’s outer layer—grown from human-derived cells

Sara Hashemi | Daily Correspondent

September 17, 2026 4:16 p.m.

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In a research lab in California, mice that look ordinary on the outside scurry around their cages. But these animals are remarkable on the inside: Roughly half of their brains are made of human nerve cells, or neurons.

Scientists transplanted lab-grown human neurons into these rodents, which were genetically engineered to lack parts of their brains. Specifically, they don’t grow the organ’s outer layer, called the cortex, which is important for things like movement, decision-making and attention. The resulting “xenocortical” mice offer a new way to study brain disorders such as schizophrenia, cerebral palsy and dementia, according to a study published in the journal Nature on September 16.

“Our goal has been to make aspects of human brain development and function accessible for investigation, so we can develop therapeutics,” says study co-author Sergiu Pașca, a neuroscientist at Stanford University, to Elie Dolgin at Science News.

Human brain diseases are notoriously difficult to study. The organ is extremely complex, containing some 86 billion neurons with trillions of connections between them, and researchers have limited access to living human brain tissue.

That’s why for more than a decade, scientists have been working on tiny replicas of the human brain called organoids. They’re often made from reprogrammed human skin cells.

Previously, Pașca and his colleagues successfully transplanted organoids into rats to study a rare genetic condition called Timothy syndrome. Most people with it also have autism and a heightened risk of epilepsy. The researchers grew some of the organoids from samples from patients with Timothy syndrome. But they were simply adding the human tissue to the rodents’ existing brain tissue, so the two were competing for space. The rodent cells’ growth outpaced that of the human cells.

This time, the researchers created a way to genetically modify mice so they didn’t develop their cortex or hippocampus, an area critical for learning and memory. When the animals were 2 days old, they received injections of organoids—each containing roughly 100,000 human-derived cells—in the empty spaces in their brains.

“Human cells that are placed in these animals will divide, will grow, and within a few weeks to a few months, they will take most of that space,” Pașca tells Antonio Regalado at MIT Technology Review.

By three months after implantation, human tissue had taken over more than 90 percent of the cortex. The cells integrated themselves into the animals’ neural wiring. Xenocortical mice also performed similarly to control creatures in behavioral tests. Meanwhile, mice that merely had brain chunks missing showed some memory problems and gait differences compared to normal animals.  

What’s more, some of the human-derived brain tissue developed into a specialized cell type known as von Economo neurons, which researchers haven’t been able to grow in the lab. These cells are some of the first to die in patients with frontotemporal dementia, a group of neurodegenerative diseases that mainly affect the cortex’s frontal and temporal lobes, areas important for personality, behavior and language.

Pașca now plans to study this form of dementia with xenocortical mice.

“We’re trying to see whether mutations that are associated with frontotemporal dementia are making the [von Economo] cells uniquely susceptible to disease,” Pașca tells Carl Zimmer and Carolyn Y. Johnson at the New York Times. “And why? Why is this happening?”

The researchers also found that the mice with half-human brains could be a good model for cerebral palsy. In people, this brain condition can be caused by oxygen deprivation during development, but mice aren’t vulnerable in the same way humans are. Nevertheless, exposing xenocortical mice to low oxygen elicited motor coordination issues similar to those seen in humans with cerebral palsy.  

“While animal models have been extremely helpful, some biological features seem to be uniquely human,” Pașca says in a statement.

As organoid research progresses, so do calls for oversight. The use of these “mini brains” raises ethical concerns for many people, including whether the tissues could gain consciousness or feel pain. To mitigate these issues, Pașca and his colleagues took several precautions while conducting their work, including extensive review by independent panels of bioethicists, reports Max Kozlov at Nature. They also designed their experiments so that the organoids were being added to mice brains that were already developed, notes Madeline Lancaster, a brain organoid researcher at the Medical Research Council’s Laboratory of Molecular Biology in England who wasn’t involved in the study.

“It’s clear that they’ve thought very carefully about the ethics here,” Lancaster tells Zoe Beketova at Science.

Sara Hashemi is a science writer and fact-checker currently based in New York City. Her work has appeared in Sierra, The Body, Maisonneuve magazine and more.