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‘Game changer’ method lets scientists peer into—and fly through—mouse bodies | Science

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A research team has turned the bodies of dead mice into vivid 3D maps of anatomy, with tissues, nerves, and vessels highlighted in color. The technique, which renders the corpses transparent and then exposes them to fluorescent antibodies that label distinct cell types, could help everything from drug development to understanding the spread of cancer, its creators and other scientists say.

The developers, at the Helmholtz Munich research institute, call their technique wildDISCO—wild because it can work on any “wild type,” or normal, mice, and DISCO for 3D imaging of solvent-cleared organs. Building on their previous success at making mouse bodies transparent, the new technique removes cholesterol from the bodies so that a vast array of existing antibodies can penetrate deep into the animals. “wildDISCO is a game changer—it allows us to see the hidden highways and byways in the body,” says Muzlifah Haniffa, a dermatologist and immunologist at the Wellcome Sanger Institute and Newcastle University’s Biosciences Institute who was not involved in the research.

The method should let scientists map a mouse at the cellular level and explore previously hidden links between tissues, like neural connections between organs, says neuroscientist Ali Ertürk, director of Helmholtz Munich, who led the work, posted recently as a preprint. His group in Germany has already posted eye-catching videos of “flying” through the 3D anatomy of a mouse with different tissues labeled.

wildDISCO can use various antibodies to map different cell types in dead mice, showing new connections between tissues and much more.Ertürk Lab/Helmholtz Munich

The method is a variation of work his team started more than a decade ago, when various scientists were developing novel ways, such as one called CLARITY, to chemically treat tissue samples and isolated organs so they became transparent and the cells inside could be seen. Ertürk and colleagues developed a similar method that made entire mouse bodies transparent. Seeking a way to pick out different cell types in the see-through bodies, they turned to nanobodies, synthetic antibodies that are much smaller than standard ones and can slip more easily into the tissue. But only a handful of nanobodies have been designed for specific cell types, limiting efforts to map the mice bodies.

So the group went looking for a way to expand its method to the thousands of standard, bigger antibodies already available commercially. Ertürk’s team found that treating mouse bodies for 2 weeks with a chemical called beta-cyclodextrin dissolves cholesterol in the cell membrane, creating spongelike holes in the whole organism without damaging other parts of the tissues. This allows standard immunoglobulin G antibodies, targeting various cell types and easily ordered from many companies, to penetrate deeply into all the mouse tissues. So far, Ertürk says his team has shown that more than 30 antibodies work with wildDISCO, including markers of the nervous system, vasculature, immune system, and proliferating cells—and the list is growing, he adds.

“This is exciting, and the immunolabeling data are quite impressive,” says Alain Chédotal, a neuroscientist at the Vision Institute in Paris who was not involved in the study. So are the fly-through visualizations of the data, he says. “This study also nicely shows that virtual reality is a great way to navigate through large 3D image data sets.”

Chédotal stresses that more work is needed for wildDISCO to reach its full potential. The preprint only shows it working with two antibodies simultaneously, allowing just two cell types at a time to be labeled. “We are working on solving this problem,” says Jie Luo, who with his Helmholtz Munich colleague Hongcheng Mai shares first authorship on the study. “We are working on using three and four antibodies at the same time.”

Still, Chédotal believes the team’s visualizations show previously unknown details of the enteric nervous system, a collection of nerve cells driving gastrointestinal functions, and some of the nodes, vessels, and organs in the lymphatic system. Next, Ertürk predicts, his team will make a complete map of the lymphatic system, which could sharpen the picture of how cancer metastasizes and how best to treat it.


A research team has turned the bodies of dead mice into vivid 3D maps of anatomy, with tissues, nerves, and vessels highlighted in color. The technique, which renders the corpses transparent and then exposes them to fluorescent antibodies that label distinct cell types, could help everything from drug development to understanding the spread of cancer, its creators and other scientists say.

The developers, at the Helmholtz Munich research institute, call their technique wildDISCO—wild because it can work on any “wild type,” or normal, mice, and DISCO for 3D imaging of solvent-cleared organs. Building on their previous success at making mouse bodies transparent, the new technique removes cholesterol from the bodies so that a vast array of existing antibodies can penetrate deep into the animals. “wildDISCO is a game changer—it allows us to see the hidden highways and byways in the body,” says Muzlifah Haniffa, a dermatologist and immunologist at the Wellcome Sanger Institute and Newcastle University’s Biosciences Institute who was not involved in the research.

The method should let scientists map a mouse at the cellular level and explore previously hidden links between tissues, like neural connections between organs, says neuroscientist Ali Ertürk, director of Helmholtz Munich, who led the work, posted recently as a preprint. His group in Germany has already posted eye-catching videos of “flying” through the 3D anatomy of a mouse with different tissues labeled.

wildDISCO can use various antibodies to map different cell types in dead mice, showing new connections between tissues and much more.Ertürk Lab/Helmholtz Munich

The method is a variation of work his team started more than a decade ago, when various scientists were developing novel ways, such as one called CLARITY, to chemically treat tissue samples and isolated organs so they became transparent and the cells inside could be seen. Ertürk and colleagues developed a similar method that made entire mouse bodies transparent. Seeking a way to pick out different cell types in the see-through bodies, they turned to nanobodies, synthetic antibodies that are much smaller than standard ones and can slip more easily into the tissue. But only a handful of nanobodies have been designed for specific cell types, limiting efforts to map the mice bodies.

So the group went looking for a way to expand its method to the thousands of standard, bigger antibodies already available commercially. Ertürk’s team found that treating mouse bodies for 2 weeks with a chemical called beta-cyclodextrin dissolves cholesterol in the cell membrane, creating spongelike holes in the whole organism without damaging other parts of the tissues. This allows standard immunoglobulin G antibodies, targeting various cell types and easily ordered from many companies, to penetrate deeply into all the mouse tissues. So far, Ertürk says his team has shown that more than 30 antibodies work with wildDISCO, including markers of the nervous system, vasculature, immune system, and proliferating cells—and the list is growing, he adds.

“This is exciting, and the immunolabeling data are quite impressive,” says Alain Chédotal, a neuroscientist at the Vision Institute in Paris who was not involved in the study. So are the fly-through visualizations of the data, he says. “This study also nicely shows that virtual reality is a great way to navigate through large 3D image data sets.”

Chédotal stresses that more work is needed for wildDISCO to reach its full potential. The preprint only shows it working with two antibodies simultaneously, allowing just two cell types at a time to be labeled. “We are working on solving this problem,” says Jie Luo, who with his Helmholtz Munich colleague Hongcheng Mai shares first authorship on the study. “We are working on using three and four antibodies at the same time.”

Still, Chédotal believes the team’s visualizations show previously unknown details of the enteric nervous system, a collection of nerve cells driving gastrointestinal functions, and some of the nodes, vessels, and organs in the lymphatic system. Next, Ertürk predicts, his team will make a complete map of the lymphatic system, which could sharpen the picture of how cancer metastasizes and how best to treat it.

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