A mouse model (also known as a murine model) is a way for researchers to study diseases in humans by using specially bred laboratory mice. Although mice are a different species, they’re mammals like humans. That means they share a lot of characteristics with humans, including many diseases.

The idea for a bone marrow transplant was originally tested in mice in the 1950s. These early studies helped develop allogeneic bone marrow transplants (transplants from a donor), which are now used to treat conditions such as leukemia, lymphoma, and other blood disorders.

However, graft-versus-host disease (GVHD) is a common and serious complication that can occur after a bone marrow transplant. GVHD can happen when the donor’s immune cells attack the recipient’s healthy tissues, mistaking them as foreign. Because GVHD remains a major challenge in transplant medicine, researchers continue to use mouse models to study how to prevent, manage, and treat the condition.

In this article, we’ll explore some key facts about the GVHD mouse model.

1. Mice Are the Most Commonly Used Animal To Study GVHD

​​While other animals, such as dogs and nonhuman primates, have been used in graft-versus-host disease research, mice are by far the most commonly used model.

Mice have played a key role in medical research for centuries. In modern research, mice were included in the Human Genome Project, a major effort to map all human genes. Through this work, scientists discovered that humans and mice share about 98 percent of their genetic material. This has helped researchers better understand both human and mouse genetics.

Mice are also easy to take care of and breed in a laboratory setting. Since mice have a shorter lifespan than humans, researchers can study how a disease or treatment affects them throughout their entire lives in a short time.

The mice used for GVHD research are specifically bred for laboratory research. While ethical guidelines require researchers to minimize unnecessary suffering, GVHD studies often involve procedures such as immune system suppression, irradiation, and disease induction, which can cause distress. In the U.S., scientists are required to follow strict protocols to balance ethical considerations with the need for accurate research results.

2. Mouse Models Are Used in Early GVHD Studies

Mouse models play a key role in the preclinical phase of GVHD research, which takes place before human clinical trials (studies that test potential treatments in people). During this phase, scientists test new treatments in animals — such as mice — to evaluate their safety and effectiveness before moving to human studies.

If a treatment shows promising results in mice, researchers can apply to the U.S. Food and Drug Administration (FDA) for approval to begin clinical trials in humans. However, because mice do not perfectly replicate human biology, additional testing in other models — such as larger animals or lab-grown human cells — is often needed before moving forward.

3. Researchers Can Closely Control Genetics in Mouse Models

The mice used to study GVHD are specifically bred for research. Because scientists have a complete map of the mouse genome (genetic blueprint), they can closely control the specific genetic traits of the mice.

The major histocompatibility complex (MHC) genes are important genetic targets for studying GVHD in mice. In humans, MHC genes provide the instructions for making human leukocyte antigens (HLAs). HLA proteins are found on the outside of most cells in the human body. These HLAs help the immune system recognize which cells belong to the body and which are foreign invaders (such as bacteria, viruses, or cancer cells). If the HLA proteins on the surface of a cell don’t match the usual pattern, the immune system will attack that cell.

When doctors check whether a donor is a good match to be a stem cell donor, they check whether the HLA proteins of the donor match the transplant recipient. This is also known as tissue typing. Finding a donor with a good HLA match is important because it can help prevent the donor’s immune cells from attacking healthy tissues in the recipient.

When studying GVHD in mice, researchers can breed mice to have a specific set of MHC genes. This allows researchers to control how closely matched the donor and recipient are. Completing a transplant between mice that are well matched or between two mice that are mismatched can give different GVHD models for studying different types of GVHD, such as acute and chronic GVHD.

4. Researchers Can Create Humanized Mice To Study GVHD

Although the immune response of mice is similar to humans, it’s not exactly the same. That means that laboratory mice can’t always accurately model human disease, including GVHD. To help mouse models more closely mimic human responses, researchers can genetically modify mice so that they share biological traits with humans. This helps scientists study how GVHD develops and how potential treatments affect the human immune system.

In transplantation research, scientists use a process called xenogenic transplantation, which involves transferring cells from one species to another. Some mice are specifically bred to accept human immune cells, making them useful for GVHD studies.

One common type of humanized mice is NSG mice. NSG mice don’t have certain types of immune cells, including T cells, B cells, or natural killer cells. This makes them unable to reject transplanted human cells. This allows researchers to introduce human peripheral blood mononuclear cells (PBMCs). PBMCs are a type of white blood cell found in the bloodstream that helps fight infections and disease. This process is called human cell engraftment.

Mice that successfully receive human PBMCs are sometimes called human immune system (HIS) mice. These HIS mice allow researchers to study how human immune cells respond to GVHD and test new treatments in a controlled laboratory setting.

5. Mouse Models Allow Researchers To Study How and Why GVHD Occurs

Researchers use mouse models to study GVHD in a controlled laboratory setting. These models allow scientists to investigate why GVHD develops and test new ways to prevent or treat it.

To create a GVHD model in mice, researchers will pick two mice with a different set of MHC genes. The recipient mouse is usually treated with total body irradiation to weaken its immune system before receiving a bone marrow transplant from the donor mouse. By controlling how closely the MHC genes match, scientists can create different GVHD models to study mild, moderate, or severe forms of the disease.

Mouse Models for Acute GVHD

A common way to study acute graft-versus-host disease is by using an MHC-mismatched model. This involves choosing a donor mouse with different MHC genes from the recipient mouse. This can mimic acute GVHD because the donor cells won’t recognize the pattern of proteins on the cells in the mouse that received the transplant. This results in the donor cells attacking healthy cells in the recipient mouse.

Mouse Models for Chronic GVHD

Studying chronic GVHD in a mouse model can be more challenging, because the disease develops over time and involves long-term immune system dysfunction. The mice used in chronic GVHD models are bred to mimic the specific type of inflammation and fibrosis (scar tissue formation) that occurs in chronic GVHD.

Autoantibody-mediated mouse models develop autoantibodies (immune proteins that mistakenly attack the body’s own tissues), similar to human chronic GVHD. This model helps scientists study how chronic GVHD leads to long-term inflammation and tissue damage.

Mouse models with sclerodermatous (pro-fibrotic) chronic GVHD develop severe scarring, where healthy tissue is replaced by stiff, nonfunctional scar tissue. This model helps researchers understand how chronic GVHD damages organs and causes long-term complications.

6. Mouse Models Have Led to Breakthroughs in Treating GVHD

Although allogeneic stem cell transplantation has been used for decades, GVHD remains a major complication. Mouse models have played a critical role in advancing GVHD prevention and treatment, leading to several major breakthroughs that have improved outcomes.

One key discovery from GVHD mouse models is T-cell depletion, a technique used to reduce the risk of GVHD. T cells are a type of white blood cell that help fight infections. In allogeneic transplants, donor T cells can attack the recipient’s healthy tissues, triggering GVHD. Research using mouse models showed that removing excess T cells from the donor stem cell sample can significantly lower the risk of GVHD while still allowing the transplant to work effectively.

Other breakthroughs in GVHD research that have come from mouse models include:

• Improved tissue typing methods to better match donors and recipients
• More tolerable conditioning regimens to prepare for a transplant
• New drugs that specifically target T cells to prevent GVHD
• The use of cyclophosphamide (Cytoxan) after transplantation for T-cell depletion

The Future of GVHD Research

Mouse models have been instrumental in advancing our understanding of graft-versus-host disease, helping researchers develop key treatments and prevention strategies. However, they have limitations, as they don’t fully replicate human immune responses, and ethical concerns remain.

To address these challenges, scientists are exploring alternative research tools, such as lab-grown tissues and advanced computer models that simulate human biology. While these emerging methods may eventually complement or even replace traditional mouse models, animal research remains essential for now as alternatives continue to develop.

Talk With Others Who Understand

On myGVHDteam, the site for people with graft-versus-host disease and their loved ones, people come together to ask questions, give advice, and share their stories with others who understand life with the condition.

Have you heard of a GVHD mouse model? What questions do you have about mouse models for GVHD? Share your experience in the comments below.