Immunology mouse models enable researchers to investigate immune cell development, activation, and effector function, as well as the dysregulation underlying autoimmune and inflammatory diseases. From T cell and B cell specific knockouts that dissect lymphocyte biology to humanized immune checkpoint models for therapeutic testing, the right model design is critical for immunological discovery and translational success.
Conditional approaches are essential in immunology research, where the same gene often has distinct functions in different immune cell populations. A gene required for T cell development may have entirely different roles in B cells, macrophages, or dendritic cells. Cell type specific conditional knockouts enable precise dissection of these lineage specific functions.
Research Applications in Immunology
Understanding Immune Function
Genetically engineered mouse models have transformed our understanding of immune system development and function. Knockout models reveal essential gene functions in lymphocyte development, antigen recognition, and effector responses. Reporter knockins enable visualization of immune cell populations and tracking of lineage relationships during immune responses.
Conditional approaches allow gene manipulation in specific immune cell types at defined developmental stages, enabling dissection of gene function without disrupting earlier developmental requirements.
Modeling Immune Dysregulation
Mouse models of autoimmune and inflammatory diseases have been essential for understanding disease mechanisms and testing therapeutic approaches. Key modeling strategies include:
Therapeutic Development
Immunology mouse models support therapeutic development across autoimmune disease, transplantation, and immuno oncology. Humanized immune checkpoint models enable direct testing of clinical antibody candidates, while cell type specific knockouts model target inhibition in relevant immune populations.
Autoimmune Disease Models
Systemic Autoimmune Disease
Models of systemic autoimmunity address diseases such as lupus and rheumatoid arthritis where multiple organ systems are affected:
- Lupus models:Knockout and knockin models affecting B cell tolerance and autoantibody production
- Rheumatoid arthritis models:Conditional knockouts in synovial and immune compartments
- Sjogren syndrome models:Models of exocrine gland autoimmunity
Organ Specific Autoimmunity
Organ specific autoimmune models focus on immune attack against particular tissues:
- Multiple sclerosis models:CNS specific autoimmunity and demyelination
- Type 1 diabetes models:Beta cell autoimmune destruction
- Autoimmune thyroiditis:Thyroid specific inflammation
- Myasthenia gravis models:Neuromuscular junction autoimmunity
Conditional knockouts enable study of gene function specifically in the target organ or in the autoreactive immune population.
Inflammatory Disease Models
Inflammatory Bowel Disease
IBD models address chronic intestinal inflammation characteristic of Crohn disease and ulcerative colitis:
- Epithelial knockouts: Study barrier function and epithelial immune responses
- T cell specific knockouts: Investigate pathogenic T cell populations
- Macrophage knockouts: Analyze innate immune contributions to colitis
- Combination models: Genetic susceptibility combined with microbial triggers
Allergy and Asthma Models
Allergic disease models address IgE mediated hypersensitivity and airway inflammation:
- Mast cell knockouts: Study immediate hypersensitivity
- Th2 pathway modifications: Investigate allergic inflammation
- Epithelial barrier models: Analyze sensitization and tolerance
- Eosinophil modifications: Study effector cell function in allergy
ingenious targeting laboratory has generated models for psoriasis, inflammatory arthritis, vasculitis, and other inflammatory diseases. Each model is designed based on the specific immune mechanisms driving the research program.
Immune Cell Specific Models
T Cell Models
T cell specific genetic manipulation enables study of T lymphocyte development and function:
| Cre Driver | Target Population | Applications |
|---|---|---|
| CD4 Cre | CD4+ and CD8+ T cells | T cell development, helper function |
| CD8 Cre | CD8+ T cells | Cytotoxic T cell function |
| Lck Cre | Early T cell development | Thymic selection |
| Foxp3 Cre | Regulatory T cells | Treg development and suppression |
| CD2 Cre | All T cells and NK cells | Pan T cell function |
B Cell Models
B cell specific models address antibody production and humoral immunity:
| Cre Driver | Target Population | Applications |
|---|---|---|
| CD19 Cre | All B cells | B cell development and function |
| CD21 Cre | Mature B cells | Peripheral B cell responses |
| AID Cre | Germinal center B cells | Affinity maturation, class switching |
| CD138 Cre | Plasma cells | Antibody secretion |
Myeloid Cell Models
Myeloid specific models address innate immunity and inflammation:
| Cre Driver | Target Population | Applications |
|---|---|---|
| LysM Cre | Macrophages, granulocytes | Innate immunity, inflammation |
| CD11c Cre | Dendritic cells | Antigen presentation |
| CX3CR1 Cre | Monocytes, microglia | Tissue macrophage function |
| CSF1R Cre | Macrophage lineage | Macrophage development |
Humanized Immune Models
Immune Checkpoint Humanization
Humanized checkpoint models express human versions of immune regulatory proteins for therapeutic antibody testing:
Single and dual checkpoint humanized models support evaluation of monotherapy and combination immunotherapy approaches.
Cytokine and Receptor Humanization
Humanization of cytokines, cytokine receptors, and other immune molecules enables testing of human specific therapeutics in an immunocompetent mouse system.
| Target | Applications | Model Type |
|---|---|---|
| PD1 | Anti PD1 antibody efficacy | Humanized knockin |
| PDL1 | Anti PDL1 antibody efficacy | Humanized knockin |
| CTLA4 | Anti CTLA4 efficacy, combinations | Humanized knockin |
| LAG3 | LAG3 inhibitor evaluation | Humanized knockin |
| TIM3 | TIM3 pathway studies | Humanized knockin |
Technical Considerations
Strain Background Considerations
Strain background significantly impacts immune phenotypes. Key considerations include:
MHC haplotype differences between strains affect antigen presentation and T cell responses. Our scientific team advises on optimal strain selection for immunological phenotyping.
Derivative Allele Flexibility
The derivative allele system provides maximum flexibility for immunology research programs:
A single project generates alleles suitable for global knockout studies, cell type specific conditional knockouts across multiple immune lineages, and reporter analysis of gene expression patterns.
Selected Publications in Immunology
Models generated by ingenious targeting laboratory have supported immunology research:
Kise M et al. (2025).
The exacerbating role of Ras guanyl releasing protein 1 in idiopathic inflammatory myopathies. ↗Clinical Immunology 282: 110636
Luo PY et al. (2025).
Autophagy of Kupffer cells modulates CD8 T cell activation in primary biliary cholangitis. ↗Gut 74(3): 496-509
Clausen BE et al. (1999).
Conditional gene targeting in macrophages and granulocytes using LysMcre mice. ↗Transgenic Research 8(4): 265-277
What Researchers Say
“The rat knock-in model from ingenious was reliable, precise, and accelerated our immunology research significantly.”
— Carla Rothlin, Professor and Director of Center of Immunology
Yale University
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Our scientific consultants are ready to discuss your immunology research requirements and recommend the optimal model design for your program. Initial consultation is provided at no charge and includes target analysis, immune cell specific Cre recommendations, and timeline estimates.
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