Why Lab Mice Don't Explain Chronic Anxiety
Before any drug comes to clinical trial with humans an exhaustive series of tests are undertaken. These pre-clinical trials are commonly undertaken using specially bred laboratory mice. Why mice? Well, despite their size, shape and habits, mice share a remarkably similar genetic profile to humans. In fact 99% of mouse genes have a human equivalent. It doesn’t stop there. Apparently diverse species to humans such as worms, flies, zebra fish, dogs and primates, share many genes and molecular pathways. This knowledge has resulted in various so-called animal models that provide a way of testing potentially life-saving drugs before going to clinical trial with humans.
Over time, genetically engineered mice have been bred in order to mimic various human diseases and health problems ranging from diabetes to cancer. Huge gains and insights into human diseases have been achieved this way but despite this many drugs appearing to work well in pre-clinical animal trials turn out to be ineffective in human trials. Not surprisingly a number of questions have been raised over the validity of animal models for mimicking human disease.
Professor’s Ehud Fonio and Ilan Golani of Tel Aviv University have raised concerns over the use of mouse models to explain chronic anxiety disorder. Using an extended experimental time period, they discovered that a strain of laboratory mice considered particularly anxious and therefore used to test anti-anxiety therapies, are not behaving in ways consistent with chronic anxiety. This, they argue, could explain why most drugs developed from this model have such poor therapeutic value in humans.
Using a hundred-times longer experimental time frame, the researchers compared the lab strain of mouse used for Generalized Anxiety Disorder (GAD) with wild mice born in activity. They discovered that while lab mice showed initial signs of anxiety when placed in stressful situations, they eventually adapted to the situation and became calm; wild mice however exhibited consistently anxious behavior. In nature, Prof. Golani explained, mice are always on high alert to protect themselves from predators.
Reporting their findings in the journals PLos One and Nature Methods, the authors argue for a complete revision of the mouse models used for testing GAD. They point to three experimental fallacies: use of the wrong animal, too short a time frame, and analysis made at the wrong points of the experiment. The authors also call for findings in one experimental laboratory to be replicated in others. They believe the inability to properly replicate findings is problematic and there is a need to develop a collaborative database, “to check for replicability of findings for scientists in isolated labs.”
American Friends of Tel Aviv University (2012, December 13). Uncovering a flaw in drug testing for chronic anxiety disorder. ScienceDaily. Retrieved January 10, 2013, from http://www.sciencedaily.com /releases/2012/12/121213132557.htm
Of mice and men – are mice relevant models for human disease? Outcomes of the European Commission workshop 'Are mice relevant models for human disease?' held in London, UK, on 21 May 2010