Have you ever thought that jellyfish and salamanders are fluorescent? Indeed they are, and proteins specific to this feature have been used to create fluorescent mouse blood. What is this used for?

Researchers at the University of Copenhagen in Denmark have devised a way to use these proteins to create fluorescent mouse blood with which they will gain new insights into brain diseases such as depression, Alzheimer’s and stroke.

The study is published in Cell Reports Methods.

Why is fluorescent mouse blood better than previously used methods?

“We have been developing a new method for visualizing blood flow in the brain in experimental mice for months,” says Hajime Hirase, professor at the University of Copenhagen’s Center for Translational Neuromedicine. He is one of the researchers behind the new method, informs Medical Xpress.

Before the newly developed method, researchers used chemical dyes instead. This dye made it possible to observe blood flow in the brain for only a few hours at a time.

Antonis Asiminas, who also worked on this method, adds that the method brings new possibilities to follow the progression of the disease over time.

“There is already evidence that blood flow is impaired in many different diseases. So it’s a tool that can be used in a lot of these, especially long-term disease progression,” he says.

Because the new method causes the mice to produce harmless fluorescent proteins to color the blood, rather than chemical dyes, the mice only need to get a single injection instead of several, and every few hours. This reduces stress and pain for the mice.

The 3 Rs

“The mouse tail has very thick blood vessels where we normally inject the dyes. Then, if we look under the microscope, we can see well-marked blood, but it only lasts for an hour or two. Our new method marks blood for months,” says Hajime Hirase.

By using fluorescent proteins instead, researchers can better implement the “3Rs,” which are principles for the ethical use of animals in research. The principles aim to improve animal testing, reduce the number of animals in research and, in some cases, replace animals entirely with other methods.

“It solves two of the three R’s. It’s both Refinement, because we reduce the stress on the animals, but it’s also Reduction, because we can do longer studies on the same animal repeatedly, so also reducing the number of animals,” explains Antonis Asiminas.

How is fluorescent mouse blood produced?

The researchers use mice because they have similar biology to humans, and there are many valuable mouse models of human disease in which researchers can use their new method.

Blood contains a large amount of albumin, a protein produced in the liver. To make mouse blood fluorescent, the researchers took the gene for a fluorescent protein and attached it to the albumin gene. This fluorescent albumin gene is then packaged into a genetically modified virus.

When mice are injected with this virus, their blood becomes fluorescent. This genetically modified virus does not cause any disease and cannot spread to other animals or humans.

“Half of the blood is made up of blood cells and the rest is a fluid called plasma. My graduate students Xiaowen Wang and Christine Delle calculated that if we label a few percent of albumin, we should be able to see fluorescent green blood through the microscope,” says Hajime Hirase.

“We package the modified genes that have the information for the albumin and the fluorescent protein into a virus that we inject into the animal. The virus enters the liver and tricks the liver into producing the modified protein that eventually makes the blood fluorescent,” adds Antonis Asiminas.

A breakthrough in understanding Alzheimer’s disease

Using a process that occurs naturally in the body, researchers can trick the livers of mice into making blood fluorescent. This makes it possible to study the blood flow in the brain.

“It’s a way for us to really study the disease in a way that we haven’t been able to do before. The aim is to give us a new perspective on the progression and development of the disease, for example in the case of stroke, and hopefully lead to a better understanding and a possible treatment”, explains Antonis Asiminas.

Leave A Reply