Following the success of making a mouse brain transparent, the Caltech researchers have discovered a new method to make an entire mouse transparent.
The research was headed by Viviana Gradinaru from the California Institute of Technology. She shares her experience in making mice transparent with the journal Cell.
To study the organs under a microscope, researchers had to dissect and slice them, studying each slice individually. It’s a time consuming process and sometimes may lead to errors.
Any imaging technique that would allow researchers to study high resolution tissue imaging without slicing would be a boon to the field.
Gradinaru previously worked on a process to try that : by replacing the lipids in a mouse brain with a transparent hydrogel called acrylamide, researchers could make them transparent. But care should be taken to ensure that the structural integrity of the organ is intact once those lipids are removed.
This works well when you are experimenting with the brain of a tiny mouse, but hydrogel can’t reach every corner of an entire mouse and an electric field can damage tissue with heat. Gradinaru and her team found a new way: they pumped the detergent through the mouse’s circulatory system. They also peeled of its skin and removed its bones that blocked the view of certain cells to get a clear picture. The detergent-dissolving technique takes about two weeks, and the transparent mouse looks like this:
This puddle of mouse is not of much interest to the naked eye, but under a microscope, it reveals the anatomy as we’ve never seen before. Staining the transparent mouse would also let scientists visualize specific tissues or cells. The above image reveals the microstructures of a kidney after it had been treated with detergent.
Studying those kidney structures would have not been so easy using conventional method like slicing tissue and reconstructing it in 3D using a computer.
“Now we are working on mapping the nervous system,” says Gradinaru. Working out exactly where nerves start and stop may help inform treatments that work by stimulating the nervous system, she says. “For example, there are instances where electrical stimulation is used to help treat Parkinson’s, bladder control or pain and those electrical stimulators are applied to nerves throughout the body. Knowing exactly where those nerves run to and from, and their functions, would improve those treatments.”
Gradinaru’s team has also applied the same technique on human tissues to detect cancerous cells in skin biopsies.