Scientists have genetically engineered mice brains to enable human cerebral tissue to take root in them, in a breakthrough that promises to boost efforts to develop treatments for diseases and developmental disorders. The rodents grafted with human brain tissue showed different behaviours from their unmodified peers, such as walking differently when subjected to oxygen shortages. The transplant technique opens the way to observing human fetal-stage neuron activity with a detail impossible to achieve in either living people or lab-grown brain tissue cultures.

Sergiu Pașca, research leader and professor at Stanford University in California, said these animal models offer a unique opportunity to study how disease-associated alterations in human brain circuitry manifest in an intact nervous system. Neuroscientists will be able to learn much more about the causes and mechanisms of neurodevelopmental and pregnancy-incurred disorders and to test possible interventions to correct or prevent them. Pașca’s team engineered and bred the mice so that almost all of their cerebral cortex — the brain’s outermost layer — was absent, according to a paper published in Nature on Wednesday.

The human tissue was grown from stem cells that were originally derived from skin and are capable of differentiating into most body cell types. The researchers exposed the engineered so-called xenocortical mice to a low-oxygen environment for five hours, mimicking a cause of cerebral palsy in humans when it occurs during pregnancy or around birth. The oxygen-starved rodents found it harder to maintain their balance and gait, while their unengineered peers were almost unaffected. Sergiu Paşca’s team engineered and bred the mice so that almost all of their cerebral cortex © Pasca lab/Stanford University The xenocortical organisms could aid better understanding of the causes of other conditions including schizophrenia, epilepsy and profound autism, Pasca said. The new technique had undergone extensive ethical scrutiny, both internally at Stanford and from external experts, he said.

Oscar Marín, professor of neuroscience at King’s College London, said the research was a “technical leap” with the “immediate prize” of “watching human cortical neurons develop, molecularly and electrically, in a far more realistic setting than a dish”. That allows benchmarking their maturation against genuine human fetal tissue, and recording the activity of large populations of human neurons in an awake animal. Marín highlighted constraints on the xenocortical technique, including that the grafted tissue did not reflect the full complexity of the human brain and that the connections being studied were human to mouse rather than human to human.