Flaws uncovered in laboratory mouse model

By Alice Campbell-Smith

The mouse is commonly used to study many human diseases from Huntington’s to breast cancer. These experiments provide important genetic clues for studying diseases, bringing us closer to developing lifesaving treatments. On first appearance the mouse may look very dissimilar to a human, yet upon cellular and DNA comparison they are strikingly similar. If these similarities are quantified we share 92 per cent of our genes with mice. So how accurately can mice represent human disease? It would seem that they provide very robust models, and conclusions drawn from experiments on mice are well regarded within the literature. Recent investigations have suggested a host of factors which could undermine that idea.

A recent study published in Nature found that wild mice and pet shop mice (known as “dirty mice”) have strong and complex immune systems which mimic those of adult humans. When lab mice were exposed to the “dirty mice” their immune systems were strengthened and more similar to that of humans.

Lab mice are kept in sterile conditions, which would not affect some work, but it is suggested that these are poor models to “mimic the human immune system.” This may be because upon encountering pathogens (disease causing microorganisms) and indeed non disease causing bacteria, throughout life and especially in our early years, our immune system becomes established and it is thought that this initial experience is crucial for future function. The importance of this is thought to be linked to allergies, which may arise as the result of inadequate exposure to beneficial bacteria during our first year of life. The mice being born into a sterile lab environment have not had the chance to gain exposure to pathogens and therefore, and it is proposed that they are not reliable model for immunology studies.

Perhaps the use of animal models in this area of biology would benefit from some re-evaluation. Alternatively, the methods could be modified. Presently, a variety of procedures can be used depending on the study. These can be divided into categories such as those that look for mutations causing disease or those using behavioural studies. Disease causing mutations can be further analysed in the lab, after initial study in the mouse, to learn about the control of how such abnormalities lead to disease. Neurological diseases can incorporate both categories, and mutations can be assessed in terms of the production of altered states of behaviour such as time taken to navigate a maze. Lastly, studies on obesity tend to observe feeding patterns.

Although these tests seem simplistic and poor predictions of the complex activities humans show, humbling as it may be the results often accurately represent what is observed in human disease.

Successful models of disease must have certain qualities, for example low maintenance costs, ease of storing and high rates of reproduction. Although widely used, the mouse is not the only model on offer. At the School of Biosciences there are studies using flies, fish, frogs and even yeast! In combination, these provide immense knowledge on how crucial biological processes work, and more importantly: what goes wrong during disease?

The future of the molecular biology of disease may rest in accurate conclusions derived from animal models. Alternatively, work could focus on cell culture owing to the advantages; allowing many more experiments to be carried out at any one time, dramatically lowering costs and avoiding ethical problems. Biomedical science is accelerating at an unprecedented rate, and what was thought to be impossible at the turn of the century has mostly been achieved. The areas which have most considerably advanced of course include cancer biology but also the study of infectious diseases. In light of emerging threats such as Zika virus, the scientific and clinical community are acutely aware that sustained efforts to control the spread and epidemic development of diseases are necessary.

Technology that is currently available means that the time in which labs can assess a new pathogen and begin to develop treatments has dramatically reduced. In the past, the pathogen had to be isolated, cultured, the DNA extracted and analysed and following this interpreted. Such procedures often took weeks or months. However, thanks to genetic tools, it is now possible to gain more information in only a few hours. This means vaccine development, (which has been recognised as the most effective form of prevention for some diseases, such as Tuberculosis) is enhanced by accurate analysis of the disease causing agent. Certainly the war with disease will continue. But science has equipped us with new and evolving tools to fight back.