The NOD mouse as a model of SLE

Area of Science:

• Immunology
• Genetics
• Autoimmunity

Background:

• Non-obese diabetic (NOD) mice spontaneously develop autoimmune diseases, including type 1 diabetes (T1D).
• NOD mice also exhibit autoimmunity to various organs and red blood cells.
• Treatment with bacillus Calmette-Guèrin (BCG) in pre-diabetic NOD mice shifts the phenotype from T1D to a systemic lupus erythematosus (SLE)-like disease.

Purpose of the Study:

• To investigate the genetic components predisposing NOD mice to BCG-induced SLE.
• To compare these SLE susceptibility genes with known T1D and SLE susceptibility genes in other mouse strains.

Main Methods:

• Review of existing literature on NOD mice genetics and autoimmunity.
• Comparative analysis of genetic factors influencing T1D and SLE in NOD mice and other lupus-prone strains (BXSB, MRL, NZ).

Main Results:

• BCG treatment induces SLE-like autoimmune rheumatic disease in NOD mice, characterized by hemolytic anemia, anti-nuclear antibodies, and glomerulonephritis.
• The reciprocal switching between T1D and SLE phenotypes suggests a shared genetic basis.
• Identification of specific genetic loci contributing to SLE susceptibility in BCG-treated NOD mice.

Conclusions:

• A single set of genes may confer susceptibility to both type 1 diabetes and systemic lupus erythematosus in NOD mice.
• Environmental factors, such as mycobacterial exposure, can modulate the autoimmune disease phenotype.
• Understanding these shared genetic factors is crucial for deciphering complex autoimmune diseases.