FEB 04, 2017 3:12 PM PST

Inflammation Monitoring Tool may Reduce Animal Experimentation Deaths

WRITTEN BY: Carmen Leitch

New work from investigators at the Graduate School of Biosphere Science at Hiroshima University may significantly impact drug testing on animals. The scientists have developed a way to assay the anti-inflammation characteristics of supplemented health foods and medicines. They identified a gene that is directly involved in the low-grade inflammation that accompanies obesity, and engineered a mouse that reports activity in that gene, creating a non-invasive assessment tool. You can learn more about this work, which has been published in Nature, from the video below.

"Animal experimentation is a serious social problem in developed countries, with many animals being sacrificed in order to develop medicines, cosmetics and functional foods for humans. What we are proposing is a way to reduce not only the number of animals which are used in experiments, but also animal experiments themselves," explained Associate Professor Noriyuki Yanaka, who led researchers at Hiroshima University in this work. 

Obesity is a global health problem, and is only on the rise. There are many physiological disorders associated with obesity, such as cardiovascular disease, some cancers and type 2 diabetes. Overfed cells get physically damaged and the immune system responds by sending in white blood cells, macrophages. That influx of macrophages has been described in numerous studies; the strained physiology of these cells is an unhealthy brew for the body, encouraging the development of deadly diseases.

Investigating that inflammation spells death for laboratory animals all over the world. The animals usually have to be sacrificed for study, which also means that many studies don't look at what is happening over years, focusing instead on short term effects and high turnover in animal colonies. 

This new method can also help reduce unnecessary deaths due to unsuccessful assessment of inflammation in fatty tissues. A reliable reporter of that inflammation has been found after investigation a number of different genes, this specific gene is highly active in fatty tissues that are seeing a lot of inflammation from the action of macrophages. The Serum Amyloid gene, Saa3, becomes active when fatty tissue is inflamed. Levels of the active gene can be measured, making a non-invasive drug testing process possible.

 Transgenic mice carrying Saa3-luc were generated (Saa3-luc mouse). Saa3-luc mice were fed either ND or HFD for 8 weeks and 16 weeks, and subjected to in vivo bioluminescence analysis / Credit: Nature Sanada et al 2017

The scientists have made a mouse that carries an Saa3 gene attached to what is referred to as a luciferase reporter. A natural gene from fireflies, luciferase can be made to emit light under specific conditions; in this case the luciferase reporter with make the Saa3 gene light up in fatty tissues that are experiencing inflammation. 

The mouse was challenged with different diets as well, one was a natural diet like way a mouse would get in the wild, the other was high in fat. The bioluminescence was detectable in living mice, and it showed high amounts of light coming from fatty tissue in obese mice. In the natural, wild fed mice, no light was detected, proving the principle of the work.

Professor Yanaka stresses that mice in laboratories will still be terminated, especially when needed for additional study. However, it can now occur at completely different time point and it could become much more selective. Yanaka predicts that the number of experimental animals required will be significantly reduced. 

Below, check out an explanation of the genetic mechanism from the Nature publication.

Saa3 gene promoter in adipocytes responds to activated macrophages via C/EBPβ signaling. Saa3 mRNA expression could be utilized for monitoring the adipose inflammatory state / Credit: Nature Sanada et al 2017

Sources: AAAS/Eurekalert! via Hiroshima University, Nature

About the Author
  • Experienced research scientist and technical expert with authorships on 28 peer-reviewed publications, traveler to over 60 countries, published photographer and internationally-exhibited painter, volunteer trained in disaster-response, CPR and DV counseling.
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