Categories of Autoimmune Disease
Autoimmune diseases arise when the immune system fails to distinguish self from non self, leading to attack on the body's own tissues. Mouse models enable controlled study of specific genetic contributions to immune tolerance and autoreactivity.
Systemic Autoimmunity
Diseases affecting multiple organ systems, including systemic lupus erythematosus (SLE), rheumatoid arthritis, and Sjogren syndrome.
Organ Specific Autoimmunity
Diseases targeting specific tissues, including type 1 diabetes (pancreas), multiple sclerosis (nervous system), and autoimmune thyroiditis.
Inflammatory Bowel Disease
Immune mediated intestinal inflammation including Crohn disease and ulcerative colitis.
Spontaneous Autoimmune Models
MRL/lpr
Mice homozygous for the lpr mutation in Fas develop severe lupus with lymphadenopathy, autoantibodies, and glomerulonephritis.
NZB/W F1
Hybrid offspring of NZB and NZW strains develop lupus like disease with anti DNA antibodies and nephritis. Female predominance mirrors human SLE.
NOD (Non Obese Diabetic)
Spontaneous development of autoimmune diabetes with insulitis and beta cell destruction. Widely used for T1D research.
K/BxN
T cell receptor transgenic model developing severe inflammatory arthritis. Serum transfer induces arthritis in naive recipients.
Key Pathways in Autoimmunity
Interferon Signaling
- •IFNAR Knockout: Interferon alpha/beta receptor knockout protects from lupus
- •STING Pathway: Links DNA sensing to type I interferon production
- •IRF Family: Controls interferon gene expression
B Cell Tolerance
- •BCR Signaling: Modulation affects autoreactive B cell fate
- •BAFF/APRIL: B cell survival factors influence persistence
- •TLR Signaling: Intrinsic TLR7 and TLR9 promote activation
T Cell Tolerance
- •Central Tolerance: Aire controls tissue restricted antigen expression
- •Peripheral Tolerance: Regulatory T cells maintain tolerance
- •Th17 Cells: IL17 producing T helper cells drive inflammation
Conditional Approaches
Tissue or cell type specific gene deletion enables dissection of contributions from different immune cell populations.
T Cell Specific
CD4 Cre or Lck Cre
Reveals T cell intrinsic requirements for tolerance
B Cell Specific
CD19 Cre or Mb1 Cre
Targets B lymphocytes for autoantibody studies
Dendritic Cell Specific
CD11c Cre
Examines antigen presenting cell contributions
Tissue Specific
Organ specific Cre
Target organ specific gene deletion for organ specific autoimmunity
Phenotyping Autoimmune Models
Serological Assessment
- •Autoantibodies: ELISA for anti nuclear, anti dsDNA, rheumatoid factor
- •Immunoglobulin levels: Total IgG, IgM, IgA quantification
- •Inflammatory markers: Cytokines, chemokines, complement
Organ Assessment
- •Kidney: Proteinuria, BUN, creatinine for lupus nephritis
- •Joints: Clinical scoring, histology for synovitis and erosion
- •CNS: Clinical scoring for EAE, demyelination histology
Immune Cell Analysis
- •Flow cytometry: Lymphocyte populations, activation markers, Tregs
- •Tissue infiltration: Immunohistochemistry for immune cells
- •Functional assays: Proliferation, cytokine production
Selected Publications in Autoimmune Research
Recent publications demonstrate the utility of genetically engineered mouse models in autoimmune disease research:
Tan L et al. (2024).
FoxO1 Deficiency in Monocytic Myeloid Derived Suppressor Cells Exacerbates B Cell Dysfunction in Systemic Lupus Erythematosus. ↗Arthritis & Rheumatology 76(12): 1834-1846
Clausen BE et al. (1999).
Conditional gene targeting in macrophages and granulocytes using LysMcre mice. ↗Transgenic Research 8(4): 265-277
What Researchers Say
“I've been working with iTL over the past 5 years in the production of 3 different genetically altered mice. Not only did iTL help in the design of the mice, but the entire process was transparent with the opportunity at any time along the way to discuss my questions or concerns with scientists who had significant insight into the process. The mice were delivered on time, as billed!”
— Raghu Mirmira, MD, PhD
University of Chicago
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