What is a Humanized Mouse? FAQs about models for immunology, immuno-oncology, and pharmacokinetics.
What is a humanized mouse model?
A humanized mouse refers to a mouse that carries some aspect(s) of human biology. For instance, “humanized” could refer to a mouse expressing a human gene introduced as a randomly integrated transgene or targeted knock-in mutation. It can refer to a mouse expressing human immune cells, tissues, tumors, microbiota, etc. Humanized could also refer to a mouse expressing a combination of the above.
By expressing human components, humanized mice more accurately recapitulate aspects of human biology compared to non-humanized mice and in vitro models. This allows for better translational modeling of human diseases and offers a more reliable platform to predict critical aspects of human responses to novel drug candidates. As a result, an increasing number of biomedical breakthroughs have utilized data from humanized mice for successful drug development and IND filing.1,2
Given their utility and value, it is safe to assume the ways to “humanize” a mouse will continue to expand as new questions and technologies arise. The Jackson Laboratory currently offers several types of humanized mouse models to support your research.
What does it mean for a mouse to be genetically humanized?
A genetically humanized mouse carries and expresses at least one human gene, replacing a mouse gene with the human equivalent. These humanized mice provide a powerful platform for investigating the function(s) of specific human genes or genetic variations in health and disease, more accurately modeling human diseases, and testing therapeutics in a model that mimics more closely human physiology and pathophysiology than traditional mouse models. Nearly one-third of the mice in our repository are genetically humanized and are ideal for in vivo studies of human immune cell development, function, and tumor biology. Learn more
What is the difference between stem-cell humanized and PBMC-humanized mice?
The CD34+ HSC humanized mouse is a model that lacks a functional murine immune system and has been engrafted with human hematopoietic stem cells (HSCs). These naïve human stem cells differentiate and mature into functional human immune cells within the mouse, creating a model that closely recapitulates key aspects of the human immune system in vivo. This platform supports long-term studies (over one year) facilitating the study of complex human immune cell interactions and the reliable testing of therapeutics with high human specificity. These immune cell humanized mice are a valuable tool for research in hematopoiesis, infectious disease, immunology, and immuno-oncology. View JAX CD34+ HSC Models
A peripheral blood mononuclear cell (PBMC) humanized mouse carries a human immune system through engraftment of mature human immune cells into a mouse lacking a functional murine immune system. Since the engrafted PMBCs matured within the human body, they recognize the mouse host as foreign and will mount a graft-versus-host (GvHD) response to mouse tissues. They can therefore be used to test potential immunosuppressive drugs for the prevention of GvHD. These mature immune cells are also capable of releasing cytokines in the presence of Immunotherapeutics or cell therapies which can be measured to predict the likelihood of those therapeutics causing a toxic response in patients, known as Cytokine Release Syndrome (CRS). View JAX PBMC Models
What mouse model supports human immune cells with less GvHD?
JAX has released a new platform NSG®-SGM3-IL15-MHC I/II DKO (S15-DKO) that expresses multiple human growth factors and is deficient in expression of mouse MHC class I and II to allow support of a wider range of human immune cells following PBMC engraftment while also greatly diminishing xenogeneic graft-versus-host disease. Once the human immune system is established, the mice are further humanized by co-engraftment of a human tumor, either a blood cancer or solid tumor. These platforms enable better modeling of the complexities of the human tumor microenvironment and provide the full systemic model needed to understand the therapies’ absorption, distribution, metabolism, and elimination in addition to therapeutic efficacy. Preclinical studies can be designed to include HSC- or PBMC-engrafted mice from multiple donors to assist in capturing donor-to-donor differences in therapeutic efficacy as well as safety.
Can you put human tumors or cell lines into mice?
JAX human tumor-bearing mice are immunodeficient NSG™ or NRG mice engrafted with human cancer cell line-derived xenografts (CDXs), or human solid or liquid tumors. JAX has a database of over 400 well-characterized solid patient-derived xenografts (PDXs), and 10 acute myeloid leukemia PDXs available for engraftment. These mice are a cost-effective, platform for proof-of-concept and target validation studies for drug development. View JAX PDX Models
What is the best mouse model to study the tumor microenvironment (TME)?
The Onco-Hu® model is a mouse co-engrafted with human immune cells and a PDX (patient-derived xenograft). This co-engraftment offers a platform that recapitulates the clinical tumor microenvironment for mechanistic investigation and a more translatable investigation of the therapeutic potential of immunomodulatory drug candidates. In these Onco-hu models, researchers can examine the interactions between human immune cells and human tumor cells, offering much greater translational validity. View JAX Onco-Hu Models & Services
How do I measure pharmacokinetics (PK) using mouse models?
A gold standard method for this is to leverage an FcRn humanized mouse - genetically engineered to exclusively express human neonatal Fc receptor (FcRn), an important recycling mechanism for regulating IgG antibody half-life. With accuracy comparable to that of non-human primate models, JAX’s FcRn humanized mice offer a fast (<14 days), accessible, and cost-effective platform to reliably predict the human pharmacokinetic (PK) profile of therapeutic antibodies. JAX has a suite of well-characterized FcRn mouse model variants to reliably support PK analysis of antibody-based therapeutics, Fc variants, and albumin conjugates which are the foundation of our HuPK portfolio. View JAX FcRn Models & Services
Can I use mice to generate humanized antibodies?
The Atlas Mouse platform is a great tool for antibody discovery: Atlas mice are genetically humanized mice that have been engineered to generate when immunized, chimeric mouse-human antibodies that contain the near full complement of human antibody gene sequence diversity. These chimeric antibodies can then efficiently be engineered into fully human monoclonal or bispecific antibody therapeutics, accelerating your antibody drug discovery and development. View JAX Atlas Mice
Can you use humanized mice in preclinical studies?
These models are ideal tools for in vivo analysis of human immune cell development and tumor response to potential therapeutics. They are an excellent alternative to studies previously performed in non-human primate models, as they are more readily available, more cost efficient, and can move studies forward more quickly. Contact the JAX Preclinical Studies Team for a consultation on your project. Our PhD-level study directors can guide you through complex projects, from model selection to IND filing.
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Related Blogs:
Immune Cell Humanized Mouse Models: PBMC Engrafted Mice
New JAX NSG portfolio strains support development of human NK cells in oncology models