World Lupus Day Spotlight: SLE Animal Models Driving Mechanistic Insights and Therapeutic Innovation

Recently, Fate Therapeutics announced that its allogeneic CAR-T cell therapy FT819, developed based on induced pluripotent stem cells (iPSCs), has been granted Regenerative Medicine Advanced Therapy (RMAT) designation by the FDA for the treatment of systemic lupus erythematosus (SLE) and its complication, lupus nephritis (LN). This significant advancement opens up new prospects for the treatment of SLE.

As World Lupus Day (May 10th) approaches, the scientific community is actively responding to patient needs by dedicating efforts to the research and development of innovative therapies, aiming to increase awareness of this often-underrecognized disease and ultimately achieve its eradication.

About Systemic Lupus Erythematosus (SLE)

Systemic lupus erythematosus (SLE) is a multifaceted, chronic autoimmune disorder characterized by aberrant immune system activation, leading to the misdirected auto-attack against the body's healthy tissues and organs. This results in systemic inflammation and potential multi-organ damage. Common clinical manifestations include dermatological lesions, arthritis, renal impairment, and neurological involvement. In severe presentations, SLE can pose a significant threat to life.

The precise pathogenesis of SLE remains incompletely elucidated; however, current understanding implicates a complex interplay of genetic susceptibility, environmental triggers, hormonal modulation, and immune system dysregulation. Owing to its intricate etiology and heterogeneous clinical presentations, significant research efforts have long been directed towards the development of more robust research models. These models are crucial for achieving a more profound understanding of the fundamental mechanisms driving SLE and for accelerating the translation of these insights into novel therapeutic interventions.

Recommended SLE Animal Models

Animal models, particularly murine models, constitute a pivotal tool in SLE research. Cyagen has established several rigorously validated models for investigating SLE, including the imiquimod-induced SLE mouse model, the pristane-induced SLE mouse model, and the MRL/MpJ-Fas mouse. These models faithfully recapitulate key pathogenetic hallmarks of human SLE, providing robust validation data and high reproducibility for preclinical investigations.

Induced Models

Exogenous agents, such as imiquimod, can rapidly elicit SLE-like immune dysregulation and pathological features. The imiquimod-induced SLE model is particularly advantageous for dissecting the mechanisms of acute disease onset and early immune responses in SLE. Furthermore, it serves as a valuable platform for screening potential therapeutic compounds and evaluating the efficacy of various interventions.

Pristane, a medium-chain alkane exhibiting adjuvant-like properties, potently induces inflammation and enhances immune activation. The pristane-induced SLE model offers significant utility in elucidating disease-specific pathogenetic mechanisms, developing targeted therapeutic strategies, and identifying promising therapeutic candidates for systemic lupus erythematosus.

Genetic Engineering Model

The MRL/MpJ-Fas knockout mouse model is generated through targeted disruption of the Fas gene within the MRL/MpJ genetic background, employing precision gene-editing technology. This model is a critical tool for investigating the role of FAS signaling in autoimmune diseases and serves as a cornerstone for elucidating the pathogenesis of systemic lupus erythematosus (SLE). Furthermore, it provides essential preclinical support for the identification of potential therapeutic targets within the FAS signaling cascade for the treatment of autoimmune disorders.

Imiquimod-Induced SLE Model

Female BALB/c mice, aged 6–8 weeks, undergo repeated topical administration of imiquimod (IMQ) on the auricles to induce systemic lupus erythematosus-like immunopathology. In treatment cohorts, prednisone is administered concurrently to assess its therapeutic efficacy.

Figure 1. Body Weight Change Curve and Clinical Phenotypes in Mice

Figure 2. Serum Anti-dsDNA Antibody Levels and Urinary Protein Analysis in Mice

Figure 3. Organ Coefficient Analysis in Mice
(Organ coefficient = organ weight/body weight × 100%)

Figure 4. Renal Pathology Analysis

Pristane-Induced SLE Model

The SLE model is established via intraperitoneal administration of pristane in BALB/c mice. By six months post-induction, the mice exhibit pronounced systemic lupus erythematosus-like immunopathology, including significant lymphadenomegaly of the inguinal lymph nodes and splenomegaly, alongside alopecia on the face and dorsum.

Figure 5. Phenotypic Changes, Lymph Nodes, Kidneys, and Spleen in Mice

Figure 6. H&E Staining

Figure 7. Anti-dsDNA Antibody Detection

Cyagen’s Extensive Autoimmune & Inflammation Pharmacology Platform

1. Efficacy Evaluation Models – Gene-Edited Models

2. Efficacy Evaluation Models – Induced Models

3. In Vitro Analysis Services for Pharmacodynamic Evaluation

Unlock crucial insights into drug efficacy, safety profiles, and mechanisms of action with Cyagen's comprehensive in vitro analysis services, expertly customized for your specific disease models, drug targets, and relevant tissue specimens. Our tailored solutions deliver critical data to accelerate your drug screening initiatives, streamline pharmacological investigations, and ultimately, empower your journey towards successful clinical translation.