‘Of mice and men’ – Brain differences require caution in lab animal tests

Image of mouse brain, from the Human Brain Atlas.
A stained image of a mouse brain features parts of the cerebral cortex. (Image: Human Brain Atlas)
Published Mar 06, 2020

The kinds of proteins in lab animals’ brains aren’t different from those of humans, but a new study shows that there are important differences in where they are located. One of the study’s leaders, KTH Professor Mathias Uhlén, says the differences warrant caution when using lab animals in the development of drugs for neurological disorders.

The findings were highlighted in the journal Science together with the release of the Human Brain Atlas.

An overview of all proteins expressed in the brain, the Brain Atlas  is based on the analysis of nearly 1,900 tissue samples covering 27 regions of the brain in three species – pigs, mice and humans. The Brain Atlas resource is the latest database to be released by the Human Protein Atlas  program, which is based at the Science for Life Laboratory (SciLifeLab), a joint research center at KTH’s Solna Campus .

Similarities and important differences

Uhlén  says that the basic brain architecture of mammals has been preserved through evolution. Yet there are considerable differences concerning neurotransmitter receptors in the species, in particular between humans and mice.

Mathias Uhlén. Professor Mathias Uhlén. Photo: Christian von Essen.

“As expected, many parts are located similarly in the mouse and human brain,” Uhlén says. “However, many proteins involved in neurological disease are found to be very differently located in the mouse and human brain.

“This means that researchers should be cautious when using animal models for drug development in neurological and psychiatric diseases.”

Uhlén is one of seven researchers from KTH who worked on the study published in Science, namely the research groups responsible for the data-handling, integration of data and AI-based systems biology. The KTH co-authors include Wen Zhong, Linn Fagerberg, Max Karlsson, Per Oksvold, Fredrik Edfors, Kalle von Feilitzen, Adil Mardinoglu[DC1].

Future implications for treatment

The new insights about protein expression in the three species could help clear the path toward development of effective drug treatments for neurological diseases such as Alzheimer, Parkinson, ALS, and bipolar disease, Uhlén says. “It is of course important for researchers to get a more holistic view of the potential target proteins for these diseases,” he says.

The research was financed by the Knut and Alice Wallenberg Foundation , and is a collaboration with China’s BGI Research Center in Shenzhen and Qingdao, as well as Aarhus University in Denmark.

SciLifeLab  research center is jointly operated by KTH Royal Institute of Technology, Uppsala University, Stockholm University and Karolinska Institutet.

David Callahan

Read the article in Science 367, eaay5947 (2020) . DOI: 10.1126/science.aay5947

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Last changed: Mar 06, 2020