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Scientists Made Mice That Are See-Through, Shrunken, and Glow in the Dark

This new technique gives scientists a whole new perspective on the body's insides.

by Bryson Masse
Aug 22 2016, 3:00pm

Image: Shutterstock

Imagine being able to peer deep inside of a creature, without needing to dissect it first. If you were studying a specific organ or tumour, that would be incredibly useful—not to mention quite a sight to behold, seeing the inner machinery of the body. Scientists have found a way to make whole animals (like lab mice and rats) transparent, and their bits and pieces fluoresce. Down the road, it could be a useful technique to map and study the human brain.

The technique is called "ultimate 3D imaging of solvent-cleared organs," or uDISCO. It basically works around the fact that mammals are filled with water and lipids—fats that block the light from filtering through an organism. Right now, scientists have to use comparatively low resolution imaging techniques, like MRI or ultrasound, to actually see inside lab animals (unless they are willing to slice the sample up into thin slivers, and put them under a microscope).

"People take a very small piece of the tissue, let's say a mouse's visual cortex, and make very thin slices, image [them] with an electron microscope, and then put [the images] together," Ali Ertürk of Ludwig Maximilians University of Munich, lead author of the new study, which is published this week in Nature Methods, explained to Motherboard over the phone. "It has very high resolution, but the issue is that it's very laborious." Mapping out an entire mouse brain in this way would be so time-consuming that it just isn't really feasible.

A lab mouse that has made transparent and shrunk with the uDISCO technique. Image: Ali Ertürk/Ludwig Maximilians University of Munich

The uDISCO technique can capture images at the cellular level. Scientists can see very complex structures as they occur in situ, and image them—capturing entire bodies, nervous systems and organs, mapping nerve connections and vascular systems.

It works by shrinking and dehydrating the animal, reducing the creature's size by up to 65 percent. This leaves protein, the main target that scientists are usually looking to investigate, which is genetically modified to glow green, and imaged using laser scanning.

Before the shrinking procedure, they anchor proteins in place. "Therefore, they don't move around," Ertürk said. Each part of specimen was shrunk the same amount, so the body stayed relatively in proportion, allowing researchers to still distinguish between a functional or nonfunctional organ.

The green fluorescent protein reveal the tiniest details in the structure of a lab mouse treated with uDISCO. Image: Ali Erturk/Ludwig Maximilians University of Munich

Applications are seriously mind-bending. Whether it's cells and their modified genes, the pathways that neurons stretch from the brain to spinal cord, or the development of transplanted stem cells, this imaging technology could allow tiny features to be directly observed.

"This will help us a lot with neuroscience, and especially diseases like Alzheimer's, Parkinson's, or MS and ALS, where the neural connectivity is lost," said Ertürk.

Ertürk was most excited about the future possibility of using this technique to study the human brain. He sees the uDISCO system as the next step towards creating an atlas of the physical connections found there. "Major methods that have been used so far can only see gross morphology. They cannot see individual neuronal connectivity. They are not going to be very helpful in mapping the neuronal anatomy of the brain," he said.

This technique also means more lab animals could be spared, as researchers would require fewer of them, continued Ertürk.

Scientists tend to focus on only a single part of the system, he explained. "I'm a neuroscientist, so I look at the brain. People working with pancreas tumors look at the pancreas," said Ertürk. "They use all of the animal to look at the single organ. The rest of the animal is wasted."

Hopefully uDISCO will help scientists shed light onto the mysteries of dysfunction and disease, but in the process we'll get a chance to see incredibly unique views of what make us tick.

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