History and Milestones of Mouse Models of Autoimmune Diseases

Abstract

Autoimmune diseases are a group of disorders mediated by self-reactive T cells and/or autoantibodies. Mice, as the most widely used animal for modeling autoimmune disorders, have been extensively used in the investigation of disease pathogenesis as well as in the search for novel therapeutics. Since the first mouse model of multiple sclerosis was established more than 60 years ago, hundreds of mouse models have been established for tens of autoimmune diseases. These mouse models can be divided into three categories based on the approaches used for disease induction. The first one represents the induced models in which autoimmunity is initiated in mice by immunization, adoptive transfer or environmental factors. The second group is formed by the spontaneous models where mice develop autoimmune disorders without further induction. The third group refers to the humanized models in which mice bearing humanized cells, tissues, or genes, develop autoimmune diseases either spontaneously or by induction. This article reviews the history and highlights the milestones of the mouse models of autoimmune diseases.

Autoantibodies against the Second Extracellular Loop of M3R Do neither Induce nor Indicate Primary Sjögren’s Syndrome

“…Due to the immune tolerance, induction of some autoantibodies requires immunization with modified antoantigens, e.g. recombinant autoantigens bearing a GST-tag, coupling of autoantigens to OVA, or heterologous autoantigens [ 27 , 28 ]. With these modifications, non-self T cell epitopes are introduced and help B cells to produce autoantibodies via linked recognition.…”

Recent Advances in Mouse Models of Sjögren's Syndrome

“…In the first phase (0-8 weeks of age), several aberrant genetic, physiological, and biochemical activities occur prior to the initiation of disease. The second phase (8)(9)(10)(11)(12)(13)(14)(15)(16) weeks of age) is characterized by inflammatory cell infiltration in exocrine glands and the production of autoantibodies and proinflammatory cytokines. Finally, in the third phase (>16 weeks of age), the function of the salivary and lacrimal glands (LG) is impaired due to autoimmune-mediated attack (18,19,57).…”

“…Similar to induced models of many other autoimmune diseases (14), the first induced model of SS was established by immunizing animals with tissue/cell extracts. In 1974, White et al reported an experimental rat model of sialadenitis induced by immunization with allogeneic submandibular gland homogenate emulsified in Freund's complete adjuvant (FCA) (111).…”

“…Animal models are invaluable tools for helping us to investigate human autoimmune diseases ( 14 ). According to the strategy of disease induction, animal models can be divided into two categories: induced models, in which disease is artificially induced in animals ( 15 ), and genetic models, in which animals develop disease symptoms spontaneously due to genetic mutations or modifications ( 16 ).…”

Mouse Models of Alopecia Areata: C3H/HeJ Mice Versus the Humanized AA Mouse Model

“…These facts alone call for clinically relevant AA research models, in which the as yet insufficiently understood pathobiology of AA can be systematically and mechanistically dissected and in which new AA treatment and prevention strategies can be explored in vivo at the preclinical level, ideally with good predictive value for the outcomes that can realistically be expected in patients with AA. Mouse models have provided invaluable research tools for dissecting the roles of extrinsic and intrinsic factors and various underlying immune pathologies in various autoimmune skin diseases (Yu et al, 2015, Yu andPetersen, 2018). Lessons that have been learned from mouse models for psoriasis (Jin et al, 2018;Mykicki et al, 2017;Nakajima and Sano, 2018), atopic dermatitis (Lin et al, 2018;Nakajima et al, 2019;Yamada et al, 2018), and vitiligo (Riding et al, 2019) have greatly advanced our understanding of disease pathogenesis and for exploring novel therapeutic strategies at the preclinical level.…”