Animal models of systemic lupus erythematosus and their applications in drug discovery

ABSTRACT

Introduction

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease with substantial phenotypic heterogeneity. Currently, our understanding of the pathogenesis is still limited, and as a result, specific and efficacious therapies are lacking. Various mouse models have been established to serve as powerful tools that will promote a better understanding of the disease and the ability to test novel drugs before clinical application.

Areas covered

The authors review the existing mouse models of SLE in terms of pathogenesis and manifestations, as well as their applications in drug discovery and development. The areas of focus include promising novel therapeutics that could benefit patients in the future and the contribution of mouse models used in preclinical studies.

Expert opinion

Given the diversity of SLE mouse models with different characteristics, researchers must select a suitable model based on the mechanism involved. The use of multiple models is needed for drug testing studies to evaluate drug efficacy on different genetic backgrounds and other mechanisms to provide a reference for clinical trials.

KEYWORDS:

• Animal model
• drug development
• lupus
• preclinical medicine
• SLE

Article highlights

• Various mouse models have been developed based on the complicated mechanism of SLE, and each recapitulates some of the human features.

• The animal models of SLE are classified into 4 categories according to the method used for construction: spontaneous, genetically modified, induced, and humanized models.

• Recent advances in our understanding of the disease mechanism have facilitated drug development, with numerous therapeutics being tested either in preclinical or clinical trials, in which mouse models have made substantial contributions.

• The most commonly used model in therapeutic testing is the spontaneous model, especially the MRL/lpr and NZB/W F1 strains, which are genetically predisposed to SLE and highly consistent with the human condition.

Given the failure to translate some new drugs from the laboratory into the clinic, researchers must select the most appropriate models for preclinical drug research based on the corresponding underlying mechanisms or pathways

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Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This study was supported by the Nonprofit Central Research Institute Fund from the Chinese Academy of Medical Sciences (2020-RC320-003).