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RIKEN Develops Transparent Mice

September 7, 2011

Researchers at the natural sciences institute RIKEN announced in the journal Nature Neuroscience that they had succeeded in developing a reagent that turns organic matter almost fully transparent. This breakthrough opens up new possibilities for far more detailed analysis of how the complex networks within our organs function.

Right: a preserved mouse embryo that has been placed in standard saline. Left: a preserved mouse embryo that has been incubated for two weeks in a solution of  sca/eA2, the reagent developed by the RIKEN team.

For biologists and medical researchers, mapping out the microscopic structures of organs is a problematic endeavor: because the majority of our organs (and those of other animals) are opaque, viewing them under a microscope requires slicing them down to just a millimeter thick. While this allows one to view the inner structures of the cells, it makes it impossible to directly observe the larger networks of cells, which have complex 3-D structures. In fact, intricate mapping work such as tracing the circuitry of the brain still has to be done largely by hand.

3-D imaging of neurons and their interconnections inside the brain of a mouse treated with sca/eA2

In his published report, researcher Atsushi Miyawaki describes how he and his team developed sca/eA2, a reagent that turns organs transparent without disrupting their shape or cohesion, and without affecting the function of genetically encoded fluorescent proteins frequently used in cell research. Already, Miyawaki’s team has used sca/eA2 to image the brains of mice embryos to a much greater depth than was previously possible, revealing a surprising level of detail in the networks of neurons, as well as allowing them to visualize the connections between the brain’s hemispheres.

3-D image of the connections between the right and left halves of a mouse brain, made visible with the sca/eA2 reagent.

One big advantage of sca/eA2 is the price tag. The reagent is made from three simple ingredients readily available in any laboratory: urea, Triton-X, a detergent used to make cell membranes more permeable, and glycerol. This puts it easily within the budget of almost any research group, opening up a wealth of new imaging possibilities. “Our current experiments are focused on the mouse brain, but applications are neither limited to mice, nor to the brain,” says Miyawaki. “We envision using Sca/eA2 on other organs such as the heart, muscles and kidneys, and on tissues from primate and human biopsy samples.”

3-D visualization of mouse neural stem cells and blood vessels.

Currently, sca/eA2 only works on dead tissue, but Miyawaki and his team are already looking into changing that. “We are currently investigating another, milder candidate reagent which would allow us to study live tissue in the same way, at somewhat lower levels of transparency. This would open the door to experiments that have simply never been possible before.”

P.S. A lot of articles, blogs and aggregators have been making a big deal of the fact that sca/eA2 uses urea (“How do you turn a mouse brain transparent? Pee on it!”). Grow up guys. If it bothers you that much, then you really don’t want to know what goes into diesel emission treatments, dish soap, cigarettes or cattle feed.

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