Researchers Breed Mice With Hybrid Brains Containing Cells From Rats

In one experiment, rat neurons helped mice restore their senses of smell—the first time any animal has perceived the world through the sensory hardware of another species

Baby mice cuddle on woodchips
To create mouse-rat "chimeras," researchers injected rat stem cells into mouse embryos that lacked some genes for brain development. Creative Touch Imaging Ltd. / NurPhoto via Getty Images

Scientists have bred mice with brains that contain working cells from rats—creating real-life “chimeras” that could teach researchers about brain development, repair and disorders, or even shed light on growing organs for transplantation. The findings were published last week in the journal Cell.

In one paper, researchers grew mice with forebrains made from rat cells, and they found the rodents developed normally. In another, they created mice with hybrid rat-mouse brains that could smell food using rat neurons.

The research is “a big step in the field,” Andrew Crane, a cell biologist at the University of Minnesota who was not involved in the work, says Scientific American’s Claudia Lopez Lloreda. “Both of these studies are answering key questions about how rat cells develop within a mouse.”

Afsaneh Gaillard, a neuroscientist at the University of Poitiers in France who did not contribute to the research, tells Science News’ Laura Sanders that the findings are “remarkable.”

“The ability to generate specific neuronal cells that can successfully integrate into the brain may provide a solution for treating a variety of brain diseases associated with neuronal loss,” Gaillard says to the publication.

Past research into “chimeras,” or hybrid creatures containing cells with different sets of DNA, has involved breeding rodents with cells from other species. Scientists have grown mice containing cells from rat pancreases or thymuses, as well as rats that have pancreas or kidney cells from mice.

But scientists had not previously been able to create hybrid brain tissue in this way. Past efforts only involved injecting brain cells or miniaturized organs into a developing or fully formed brain.

In the new research, however, the teams developed hybrid brains by injecting rat stem cells into early-stage mouse embryos that lacked certain genes for brain development.

For one of the papers, the researchers knocked out genes in mice responsible for the development of the forebrain, which plays a role in cognition, sensation and voluntary movement. When the researchers bred mice without forebrains, they died shortly after birth, according to Nature News’ Sara Reardon.

But when the mouse embryos were injected with rat stem cells, the mice developed with forebrains made from rat cells.

“The chimeras can live a normal life, up to two years that we analyzed,” Jun Wu, a co-author of both studies and molecular biologist at the University of Texas Southwestern Medical Center, says to Science News.

In the other study, the researchers genetically silenced or killed neurons that mice use to smell. Without these neurons, the mice couldn’t find cookies hidden in their cages. Next, scientists injected rat stem cells into mouse embryos that had the same smelling genes deactivated. Once they were born, those mice were able to sniff out the cookies using the rat neurons.

That achievement marks the first time an animal has used the sensory hardware from another species to respond to the world, according to a statement from Columbia University.

Both papers have implications for understanding and treating brain diseases.

“This has a great opportunity for human health, where we can understand better how to make cell replacement therapies for humans,” Kristin Baldwin, a co-author of the study and a neuroscientist at Columbia University, tells New Scientist’s Tom Leslie. “We can also make models in a mouse or rat of diseases that affect longer-lived organisms.”

In both studies, the rat cells developed at the same rate as the mouse cells, despite the fact that rats develop more slowly than mice. Jian Feng, a physiologist at the University at Buffalo who did not contribute to the findings, tells Nature News that he wasn’t surprised by this result. “There’s lots of fascinating biology to be learnt from this [rat-mouse] chimera,” he says to the publication.

Such synchronization will be key to future research on organ development, which could be used to grow organs for transplants.

“In the future, if we want to make human organs in a large animal like a pig, we need to synchronize cells’ development so that the cells match one another during the developmental process,” Walter Low, a neuroscientist at the University of Minnesota who wasn’t involved in the work, tells Scientific American.

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