Animal models in autoimmune diseases: lessons learned from mouse models for Sjögren's syndrome

Abstract

The mouse model is the one of the most frequently used and well-established animal models, and is currently used in many research areas. To date, various mouse models have been utilized to elucidate underlying causes of multifactorial autoimmune conditions, including pathological immune components and specific signaling pathways. This review summarizes the more recent mouse models for Sjögren's syndrome, a systemic autoimmune disease characterized by lymphocytic infiltration in the exocrine glands, such as the salivary and lacrimal glands, and loss of secretory function, resulting in dry mouth and dry eyes in patients. Although every Sjögren's syndrome mouse model resembles the major symptoms or phenotypes of Sjögren's syndrome conditions in humans, the characteristics of each model are variable. Moreover, to date, there is no single mouse model that can completely replicate the human conditions. However, unique features of each mouse model provide insights into the roles of potential etiological and immunological factors in the development and progression of Sjögren's syndrome. Here, we will overview the Sjögren's syndrome mouse models. Lessons from these mouse models will aid us to understand underlying immune dysregulation in autoimmune diseases in general, and will guide us to direct future research towards appropriate diagnostic and therapeutic strategies.

Figure 1

Schematic illustration of etiopathogenic factors involved in Sjögren’s syndrome. Mouse models are listed under the categories of etiological factors in this figure. A mouse model used to study one etiological factor does not necessarily exclude a possibility of involving other etiological factors. Factors of secretory dysfunction, such as immune cell infiltrates and anti-M3R autoantibodies, are included in this figure. Anti-M3R autoantibodies are known to block the binding site of receptor for acetylcholine, resulting in inhibition of fluid secretion from the acinar cells. Ach, acetylcholine; M3R, muscarinic type 3 receptor; Abs, autoantibodies; SMX, salivary glands