Scientists have created whole see-through mice, which could pave the way for better understanding of human illness.
Image credit: Yang, et al., California Institute of Technology
The researchers, including senior study author Dr. Viviana Gradinaru, assistant professor of biology at the institute, recently published their findings in the journal Cell.
Mice have been used in medical research since the early 20th Century, primarily because their genetic makeup is very similar to that of humans.
As such, the researchers say the development of these transparent critters may lead to a better understanding of interactions between the human brain and body, improved accuracy in disease diagnosis and monitoring, and could even lead to new treatments for an array of medical conditions, such as autism and chronic pain.
In order to gauge a better understanding of complex cellular interactions, which are critical to numerous biological processes, scientists need access to 3D maps of intact organs and bodies. But in the past, techniques for making bodies and organs transparent - which allows for imaging and subsequent generation of 3D maps - have been limited to embryos and the brain.
Whole see-through mice created within 2 weeks
In this latest study, Dr. Gradinaru and colleagues modified a brain-clearing technique they previously created, called CLARITY. This is a method that involves inserting tissue into hydrogels as a way of preserving its 3D structure and crucial molecular information. Detergents are then applied to extract lipids from the tissue, making it transparent.
To apply the technique to whole organs and bodies of mice, they essentially sped up the process. After euthanizing and removing the skin of the mice, they used a method called passive CLARITY technique (PACT) to pinpoint the hydrogel that was most effective for rapid removal of lipids from tissue.
They then used a novel procedure called perfusion-assisted agent release in situ (PARS) to speed up the clearing process while avoiding tissue damage. In PARS, the hydrogel and clearing reagents are delivered directly to the bloodstream of the rodents.
The researchers found that the reagents made the organs of the mice - including the heart, lung, kidney and intestine - opaque in 2-3 days, while the brains and whole bodies of the mice became transparent within 2 weeks.
In addition, the team created a technique for refractive index matching solution (RIMS). This allows scientists to store the cleared tissue long-term, and use a standard confocal microscope to closely analyze it.
Commenting on the team's creation, Dr. Gradinaru says:
"Although the idea of tissue clearing has been around for a century, to our knowledge, this is the first study to perform whole-body clearing, as opposed to first extracting and then clearing organs outside the adult body.
Our methodology has the potential to accelerate any scientific endeavor that would benefit from whole-organism mapping, including the study of how peripheral nerves and organs can profoundly affect cognition and mental processing, and vice versa."
Last year, Medical News Today reported on a study by researchers from the University of California-Riverside, which detailed the creation of a transparent skull implant that could pave the way for new treatments for neurological disorders.