2 3 As science and medicine progressed, transgenic techniques, gene knockout techniques, inducible knockouts and humanised mouse models were developed that allowed further insight into the role of a single gene or molecule in lupus pathogenesis. 1 For the last four decades, we have characterised spontaneous murine models of lupus that were defined genetically and immunologically and served as the initial step in supporting or not the progress of new treatments to clinical trials for lupus. Perhaps more so in lupus than any other human disease, mouse models have contributed significantly to our understanding of the disease and the development/testing of new treatments for the disease. This step-by-step model has resulted in most of the major breakthroughs in new treatments for disease. Research into human diseases spans in vitro assessments to preclinical animal models of disease to in vivo human assessments and finally testing of therapeutics in humans. These limitations, however, do not marginalise the importance of animal models nor the significant contributions they have made to our understanding of lupus. Thus, proving a therapy or mechanism of disease in one mouse model is similar to proving a mechanism/therapy in a limited subset of human lupus. Finally, the heterogeneous aspects of human lupus, both in clinical presentation, underlying pathogenesis and genetics, are not completely represented in current mouse models. Efficacy and toxicity of compounds can vary significantly between humans and mice, also limiting direct translation. Although similar, mouse and human immune systems are different and thus one cannot assume a mechanism for disease in one is translatable to the other. Despite their utility, mouse models of lupus have their distinct limitations. ![]() These mouse models of lupus have contributed significantly to our knowledge of the pathogenesis of lupus and served as valuable preclinical models for proof of concept for new therapies. There are spontaneous models of lupus, inducible models of lupus, transgenic-induced lupus, gene knockout induced lupus and humanised mouse models of lupus. ![]() There are perhaps more applicable murine models of lupus than any other human disease. Animal models of human diseases are an invaluable tool for defining pathogenic mechanisms and testing of novel therapeutic agents. Lupus is a complex heterogeneous disease characterised by autoantibody production and immune complex deposition followed by damage to target tissues.
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