An update on lupus animal models

Abstract

Purpose of the review The complexity and heterogeneity of the clinical presentation in systemic lupus of erythematosus (SLE), combined to the inherent limitations of clinical research, have made it difficult to investigate the etiology of this disease directly in patients. Various mouse models have been developed to dissect the cellular and genetic mechanisms of SLE, as well as to identify therapeutic targets and to screen treatments. The purpose of this review is to summarize the major spontaneous and induced mouse models of SLE and to provide an update on the major advances they have contributed to the field. Recent findings Mouse models of SLE have continued to contribute to understand the cellular, signaling and metabolic mechanisms contributing to the disease, and how targeting these pathways can provide therapeutic targets. Whenever possible, we discuss the advantage of using one model over the others to test a specific hypothesis Summary Spontaneous and induced models of lupus models are useful tools for the study of the etiology of the disease, identify therapeutic targets and screen treatments in pre-clinical studies. Each model shares specific subsets of attributes with the disease observed in humans, which provides investigators a tool to tailor to their specific needs.

The Lupus Susceptibility Locus Sgp3 Encodes the Suppressor of Endogenous Retrovirus Expression SNERV

“…NZB-and NZW-based lupus models are widely used in pre-clinical drug-efficacy trials because they recapitulate more clinical features of human SLE than other mouse strains (Celhar and Fairhurst, 2017;Li et al, 2017). Of the few drugs approved for treatment of SLE by the FDA, essentially all-systemic immunosuppressants, antimalarials, anti-BAFF, anti-CD20, anti-CTLA-4, interferon-alpha blockade, and toll-like receptor antagonists-were tested pre-clinically in NZB/W models (Celhar and Fairhurst, 2017).…”

Tolerogenic dendritic cell transfer ameliorates systemic lupus erythematosus in mice

“…The lack of T-cell depletion effect of tolDCs could be related to the intense systemic lymphoproliferation that occurs in both of these strains. [42][43][44] Treg cell expansion has also been described as a mechanism associated with the modulatory function of tolDCs, 45-48 but we did not detect an expansion of Treg cell number in the kidney or spleen from MRL-Fas lpr mice (Fig. 6a,e).…”

Development of an IL-17A DNA Vaccine to Treat Systemic Lupus Erythematosus in Mice

“…In this study, we utilized two mouse strains, NZBWF1 and MRL/lgr, as models of SLE. The MRL/lgr mouse strain has shown more rapid and severe disease development than the NZBWF1 mouse strain [22,23]. We speculate that the different responses to the IL-17A vaccine between the two strains might be due to the severity of the disease model.…”