Lewis rats are a laboratory rat strain commonly used in biomedical research. They serve as valuable models for studying human diseases, particularly those involving the immune system. Their consistent genetic makeup and predictable responses make them suitable for investigating disease mechanisms and evaluating potential treatments.
Defining Characteristics of Lewis Rats
The Lewis rat strain originated from Wistar stock in the early 1950s, developed by Dr. Margaret Lewis. They are an inbred strain, meaning they possess a highly uniform genetic background, which contributes to consistent experimental results. These rats are typically albino and are docile.
Lewis rats are inherently susceptible to developing induced autoimmune diseases. This susceptibility is linked to their immune system profile, including a hyporeactive hypothalamic-pituitary-adrenal (HPA) axis and lower baseline levels of corticosterone, which can impact immune regulation. Their major histocompatibility complex (MHC) haplotype, RT1l, contributes to their unique immune responses.
Primary Applications in Scientific Research
Lewis rats are extensively used to model human autoimmune conditions due to their specific immune characteristics. One prominent application is in studying Experimental Autoimmune Encephalomyelitis (EAE), a model for multiple sclerosis. EAE is typically induced by immunizing Lewis rats with central nervous system antigens like myelin basic protein (MBP), leading to acute paralysis and inflammation. This model allows researchers to investigate the roles of T cells and macrophages in disease initiation and recovery.
Another significant application is in modeling rheumatoid arthritis through Adjuvant-Induced Arthritis (AIA). Lewis rats are highly susceptible to AIA, which is induced by injecting a suspension containing Mycobacterium tuberculosis. This leads to chronic inflammation, joint damage, and bone resorption, mimicking features of human rheumatoid arthritis. Consistent arthritis development provides a reliable system for testing anti-inflammatory agents.
Lewis rats also serve in transplantation immunology research, specifically for studying graft rejection. Their use helps to understand immune responses against transplanted tissues and explore strategies to promote transplant acceptance. They are utilized in models of inflammatory bowel disease (IBD) induced by agents such as 2,4,6-trinitrobenzene sulfonic acid (TNBS) or dextran sodium sulfate (DSS), providing insights into gut inflammation. They are also used in experimental autoimmune uveitis (EAU) and streptozotocin (STZ)-induced diabetes models.
Advancing Medical Understanding
Research using Lewis rats has significantly advanced understanding of complex autoimmune disease mechanisms. By studying EAE, scientists have gained insights into the T-cell mediated inflammation and neurobiology involved in conditions like multiple sclerosis. This has helped identify specific immune cell types, such as CD4+ Th1 cells and M1 macrophages, that drive disease progression, as well as M2 macrophages and regulatory T cells that contribute to recovery. These findings inform the development of therapies targeting specific immune pathways.
Studies in Lewis rats with AIA have clarified the inflammatory processes in arthritis, including the roles of cytokines like TNF-alpha, IL-1beta, and IL-6. This detailed understanding of disease pathology has supported the evaluation of various anti-arthritic compounds. Their consistent disease induction allows for reliable preclinical testing of new drug candidates before human clinical trials.
Lewis rat models also aid in identifying potential therapeutic targets for autoimmune and inflammatory conditions. By observing how different interventions impact disease progression in these rats, researchers can pinpoint specific molecules or pathways to modulate for treatment. This accelerates the translation of basic scientific discoveries into clinical applications, ultimately benefiting patients with these challenging diseases.