EARA | Animals - Small mammals

Besides mice and rats, a diverse group of small mammals - from rabbits to naked mole rats - provide valuable insights into human health challenges ranging from COVID-19 to cancer resistance.

Small mammals play an important role in biomedical and health research, supporting advances in medicine, public health and veterinary care. While mice and rats are the most widely used species, a range of other small mammals, including rabbits, guinea pigs, hamsters, ferrets and certain wild species, offer biological characteristics that make them particularly valuable for studying specific diseases, body systems and treatments.

These animals are used across many areas of research, from infectious diseases and respiratory conditions to hearing loss, cardiovascular disease and reproductive health. In some cases, their physiology or immune responses more closely resemble those of humans than those of mice and rats, allowing researchers to answer questions that cannot be addressed using other methods alone.

This feature explores how and why small mammals are used in research, the scientific areas in which they contribute most, their limitations and how their welfare is safeguarded.

Why are small mammals used in research?

Small mammals are used in biomedical research because their biology allows researchers to study disease mechanisms, test treatments and evaluate safety in ways that are not possible using non-animal methods alone.

Compared with larger animals, small mammals are easier to house and care for, reproduce relatively quickly and have well-characterised biology. Compared with mice and rats, some species (e.g., rabbits, guinea pigs and hamsters) have anatomical, physiological or immunological traits that are closer to those of humans for specific organs or diseases.Unlike mice, small mammals are rarely genetically engineered at scale. Instead, they are often chosen because they naturally replicate key aspects of human disease, such as airway responses, immune reactions or sensory systems.

Small mammals are also larger than mice and rats, making them a more suitable animal to study certain parts of the body, such as the eyes. This is also why rabbits are often preferred over rodents for studies into reproduction, because their uteruses are larger and easier to study.

Lear more about the use of mice in research in our feature.

Which areas of research use small mammals?

Infectious diseases

Several small mammals are naturally susceptible to infectious diseases that also affect humans, making them valuable for studying how infections spread, how the immune system responds and how treatments and vaccines work.

Small mammals played a crucial role in Covid-19 research and vaccine development.  Syrian hamsters, in particular, can be infected naturally with SARS-CoV-2 and develop symptoms similar to those seen in people, including lung damage and changes to the sense of smell. This makes them a useful model for studying disease mechanisms and comparing the effects of different virus variants, such as the Omicron strain.
Because hamsters reflect key aspects of human disease, they have also been used to assess potential treatments. For example, researchers from the Free University of Berlin, Charité – University Medicine Berlin, and the Max Delbrück Center, tested a nasal vaccine in hamsters that targets the mucosal surfaces of the nose, throat and lungs. This approach aims to strengthen immune protection at the site of infection and is now being prepared for trials in humans. The same German team has also used hamsters to provide insights into early mechanisms leading to lung inflammation in Covid-19, contributing to understand why Covid-19 severity varies between patients.
Hamsters are larger than mice, which makes their internal organs easier to visualise, particularly when assessing the effects of the coronavirus on the lungs. Even before the Covid-19 pandemic, hamsters were already used to investigate severe acute respiratory syndrome (SARS), another respiratory disease caused by a different coronavirus, that was responsible for a global outbreak in 2003.
Ferrets are also important animals for infectious disease research. Their lungs function in a way that is more similar to human lungs than those of mice or rats, allowing researchers to study respiratory infections such as influenza and Covid-19, as well as how viruses spread between individuals. For example, a study at Erasmus MC, Rotterdam, Netherlands, and Columbia University, USA, used ferrets to test and validate a nasal spray that prevents the Covid-19 virus from entering cells. 

Ferrets have also contributed to influenza research. Scientists at the Johns Hopkins Bloomberg School of Public Health showed that exposure to seasonal flu viruses could provide partial protection against severe disease following infection with H5N1 in ferrets. This work helps researchers better understand the role of flu antibodies in human immunity and vaccination strategies.
Guinea pigs and humans have similar immune systems, making them a suitable species for investigating how infections take hold and affect the body. This has helped to identify different routes to transmission – for example in a study at the University of California, Davis, USA, it was shown that viral droplets of influenza, which allow the virus to spread through the air, can also be transmitted by attaching to dust.
Guinea pigs are also highly susceptible to infections by a range of bacteria, or viruses, that also infect humans, including Mycobacterium tuberculosis that causes tuberculosis. Historically, research involving guinea pigs contributed to the development of streptomycin, the first effective antibiotic treatment for tuberculosis, as well as for plague and pneumonia.
Mongolian gerbils are susceptible to several bacteria, viruses and parasites that also infect humans, such as Helicobacter pylori which is responsible for various typesof stomach infection and ulcers. Studying how these infections develop in gerbils helps researchers identify disease mechanisms and test potential treatments.

Other research areas

Guinea pigs are considered one of the most suitable animals to study asthma because their airways respond to allergens in a way that closely mirrors human asthma, including both early and late-phase reactions. Early studies in guinea pigs revealed how chemical nerve signals control airway muscles, paving the way for the development of modern asthma inhalers that relieve breathing difficulties.
Guinea pigs are also sensitive to certain allergens, making them useful for studying allergic skin reactions and severe responses such as anaphylactic shock, which can be triggered by foods, medicines or insect stings.
In addition, research using guinea pigs has shown how environmental factors, like air pollution, can affect the lungs and worsen respiratory disease. A study at Imperial College London demonstrated that exposure to diesel fumes in guinea pigs, can damage the lungs and exacerbate conditions such as asthma.

Small mammals have made important contributions to research on hearing and vision.
Guinea pigs are especially suited to research hearing loss, because the structure of their ears is similar to that of humans. A recent European Research Council project, at the Middle East Technical University, in Ankara, Turkey, has developed a fully implantable cochlear implant for people with hearing problems. It made use of hearing-impaired guinea pigs as part of its work to show that sound waves could recharge the device and make it more convenient for users. This research is now being followed up with further research, using guinea pigs, to develop a way to recharge implants using a wireless device.
Mongolian gerbils can hear a similar range of sounds to humans, which has made them valuable in studies of hearing loss. At the University of Sheffield, UK, researchers used gerbils to test a stem cell treatment that successfully restored hearing. In another study at Rockefeller University, Scientists maintained living cochlea from gerbils in a specialised chamber, allowing them to directly observe how sound processing works and to test potential treatments for hearing loss.
Rabbits, due to their large eyes, are widely used in eye research. Their size allows easier access to eye tissues and more accurate testing of treatments. For example, a study led by Purdue University, USA, showed that drugs could be delivered to rabbits’ eyes using contact lenses, treating eye disease while reducing discomfort.

Some small mammals have unique biological traits that make them particularly useful for brain research.
Hamsters are hibernating animals, and researchers are studying this natural process to understand how synapses, the connections between neurons, can be lost and later restored. At VIB-KU Leuven, Belgium, scientists are investigating how hamsters re-establish lost synapses during hibernation, with the aim of gaining insights into neurodegenerative diseases such as Alzheimer’s.
The prairie vole has been a key research animal for shedding light on social bonding and relationships since they usually mate for life, which is unusual for rodents. Through the study of this unique species, researchers have managed to understand the neural basis for love, as well as look at the effect of alcohol and other addictive substances on social relationships.

Naked mole rats are known for their remarkably long lifespans, as well as resistance to cancer, and this has cemented them as a key component of anti-ageing research. A team at the University of Rochester, US, showed that the lives of mice could be extended by transferring a single gene from naked mole rats. Meanwhile, researchers at the University of Cambridge, UK, found that the interactions between the cells and molecules with their environment in naked mole rats may be what prevents cancer from developing into tumours in the animals, instead of an intrinsic inability of the cells to multiply and give origin to cancer. This finding has changed researchers’ perspective on cancer resistance.

Small mammals are frequently used to test medical devices and regenerative treatments before they are used in people. They are preferred to rodents such as mice and rats because they are larger and, in some cases, their size allows testing devices that could be applied to humans.
Rabbits were used to test a ‘pumping’ patch of heart tissue, developed by Imperial College London, UK, to repair damage after a heart attack. Successful results in rabbits have already paved the way for human trials.
At the University of Liège, Belgium, researchers and cardiologists used rabbits to test the safety of a new plastic material, Poly Hydroxy-Oxazolidone (PHOx), designed for medical devices. The material showed no signs of inflammation or rejection and could be used to produce personalised implants, such as heart valves tailored to individual patients.

A major research area involving rabbits is the production of antibodies — proteins that help the immune system recognise and neutralise harmful substances. Antibody-based therapies are often more specific and less toxic than many traditional drugs.
Rabbits are particularly suitable for this work because their larger size allows greater quantities of antibodies that can be easily obtained by taking blood or serum under anaesthetic. Also, the rabbit immune system can recognise a wider range of foreign or toxic targets (called antigens) than that of many rodents, including targets that closely resemble those found in humans. 
In some cases, rabbits are essential for the development of specific therapies. One example is thymoglobulin, a polyclonal antibody derived from rabbit serum that is used to prevent immune rejection in organ transplant patients.
Although technologies to produce antibodies with non-animal methods are advancing rapidly, most antibodies used for therapeutic purposes in both human and veterinary medicine still need to be produced using animal hosts. This is because animal-derived antibodies rely on the natural complexity of living immune systems, which cannot yet be fully replicated by laboratory-based methods. As a result, they remain critical tools across the biomedical sector, from basic research to the development of life-saving medicines. Animal-derived antibodies are also particularly important in veterinary medicine, where treatments must be tailored to a wide range of species.
See also our feature, The vital role of antibodies in biomedical research, and the EARA/EFPIA report on animal-derived antibodies, submitted to the European Commission to highlight the continuing importance of this use of animals in research.

Research using small mammals also seeks to improve the health and welfare of animals themselves. In rabbits, this includes efforts to prevent and treat severe viral diseases such as myxomatosis, which only infects rabbits, through the development of vaccines and other treatments. Thanks to studies and tests in rabbits, vaccines were also developed for rabbit haemorrhagic disease, which affects pet and wild rabbits alike. 
In addition, rabbits have been used to test new blood substitutes that can safely deliver oxygen during severe blood loss, with potential use in both veterinary and human medicine.
Veterinary research in guinea pigs has similarly provided valuable insights for their care. Studies on incisor and cheek tooth growth showed that diet alone does not fully explain dental disease, highlighting the importance of genetic and mineral factors for preventing common dental problems in pet guinea pigs and other rodents.

How are small mammals taken care of?

Many small mammals used in research are domesticated species that are also commonly kept as pets. As a result, their behaviour, care needs and welfare requirements are well understood. In research facilities, housing and husbandry are designed to support natural behaviours, reduce stress and promote both animal wellbeing and reliable scientific outcomes.

Animals are cared for by trained staff and regularly monitored by veterinarians. Environmental conditions such as temperature, lighting, noise and hygiene are carefully controlled. Social housing, environmental enrichment, gentle handling and positive human-animal interactions are central to laboratory animal care. Supporting animals’ physical and psychological needs improves wellbeing and leads to more reliable and reproducible scientific results.

Rabbits are social, intelligent animals and are typically housed in pairs or compatible groups in spacious floor pens with soft bedding. They are provided with enrichment that encourages natural behaviours such as foraging, hiding and chewing, including hay, tunnels, chew toys and digging substrates. Rabbits are accustomed to human contact from an early age and are often trained using positive reinforcement to cooperate with routine procedures. Temporary single housing may be used after surgery but is kept to a minimum.

Guinea pigs are highly social and are housed in compatible groups. Their enclosures provide space for movement and social interaction, with solid floors and dust-free bedding to protect foot health. Because guinea pigs are naturally cautious, housing includes sheltered areas where they can hide. Hay is essential for both nutrition and enrichment, and fresh fruit and vegetables are provided to supply vitamin C, which they cannot produce themselves.

Hamsters are housed in environments that allow nesting, burrowing and foraging. Deep bedding and nesting material enables them to create enclosed sleeping areas, while gnawing materials support dental health. Housing conditions are carefully controlled, as hamsters are sensitive to light, noise and temperature.

Ferrets are active and curious animals housed in compatible social groups. Their enclosures provide space, height and varied enrichment such as tunnels, hammocks and nesting areas to support play and exploration. Many ferrets enjoy playing in water; a shallow water bath can be a good form of enrichment.

Gerbils live in stable family groups and are provided with deep substrate for digging and tunnel-building. Housing supports natural behaviours while minimising noise and disturbance. Gnawing materials and suitable surfaces help maintain dental and claw health, and animals are habituated to gentle handling from a young age.

Limitations of small mammals as animal models for biomedical research

Like all research models, small mammals do not perfectly replicate human biology. Differences in lifespan, metabolism, immune responses and disease progression mean that findings from animal studies cannot always be directly translated to humans. To address these limitations, biomedical research rarely relies on a single species. Instead, different animal species and non-animal approaches are used in a complementary way, with each chosen for the specific biological features that best match the research question. For example, while mice are often used for early-stage studies, other small mammals may be more suitable for investigating immune responses, lung function, sensory systems or disease transmission, where their biology more closely resembles that of humans. For certain research questions, particularly when studying complex brain function, advanced cognition or immune responses that are highly similar to those of humans, research may also need to be confirmed in non-human primates before moving into clinical trials, as their physiology and immune systems can provide critical validation that cannot be obtained from small mammals alone.

Replacement, reduction and refinement

In line with the principle of replacement, significant progress has been made in developing New Approach Methodologies (NAMs) that pose as alternatives to tests that have traditionally used small mammals.

For example, alternatives to tests that induce fever to understand if a substance is pyrogenic (fever-inducing) and skin and eye irritation tests, used to assess if a substance could damage the skin or eyes, are increasingly being developed and implemented. These include in vitro assays using human cell cultures, reconstructed tissues and computer modelling approaches, which can reduce animal suffering and, in some cases, provide results that are more directly relevant to human biology. The long-term goal of this work is to fully phase out these animal-based tests wherever scientifically and regulatorily possible.

Ways are also being sought to replace small mammals used in research with different, non-mammal species, such as fish or insects, which are more readily available in the numbers needed to carry out valid biomedical research.

Replacement also includes the use of animal-derived biological tools that no longer require live animals. A key example is the use of cells from the ovaries of Chinese hamsters, which have been used to create a cell line that is now an invaluable biological tool for carrying out genetic manipulation to make cells produce important commercial drugs such as antibodies and proteins.

This cell line has had widespread use in many areas of research, particularly genetics and molecular biology, and, as such, has been the standard for growing the cells of mammals in the lab for decades. What makes Chinese hamsters the ideal animal to use for this purpose is the similarity of their cells to ours, and therefore their relevance to numerous human applications, for example to produce drugs for cancer. These cells are also easy to keep in the laboratory and to grow many cells at once.

Where the use of animals remains necessary, extensive procedural refinements are applied to minimise any potential harm and improve welfare. Injections and blood collection are refined by using the smallest appropriate needles, minimally invasive techniques and trained personnel to reduce stress and pain. Peripheral veins are used wherever possible, rather than the jugular vein, and analgesia or anaesthesia is provided when appropriate.

For surgical procedures, refinements focus on reducing invasiveness, improving physiological stability and enabling faster recovery. Less invasive techniques, such as laparoscopic surgery are used whenever feasible, alongside careful anaesthetic management, precise surgical skills and comprehensive post-operative care.

In rabbits, an optimised anaesthetic protocol, developed by the Hokkaido University in Japan, has been shown to provide smooth induction, maintain spontaneous breathing and allow faster recovery compared with older methods. In guinea pigs, refinements such as reducing isoflurane levels or selecting sedatives that minimise cardiorespiratory depressionhave significantly improved stability during longer surgical procedures.

Handling and restraint are particularly important for rabbits, which are prone to back and leg injuries if handled incorrectly. Staff are trained to handle rabbits, namely using appropriate restraint methods such as towel wraps, supportive holds or specialised devices, and efforts are made to minimise unnecessary handling.

Other useful sources

Hamster Housing & Handling, The 3Rs collaborative

Rabbit Refinements, The 3Rs collaborative

The reality of rabbit research, Understanding Animal Research

Environmental Enrichment for Guinea Pigs, University of Washington

Enhancing Gerbil Welfare Through Positive Reinforcement Training in Research Environments, JOVE