Systemic Lupus Erythematosus Animal Model Development Services
The chronic and complex disease Systemic Lupus Erythematosus (SLE), like every other autoimmune disease, is the result of genetic, epigenetic, and environmental factors. At Protheragen, we are dedicated to providing high-quality, customized animal model solutions that meet the diverse needs of our clients. With our experienced team, state-of-the-art facilities, and commitment to excellence, we are well-positioned to support the global research community in the fight against SLE.
Overview of Systemic Lupus Erythematosus Animal Models
Systemic Lupus Erythematosus (SLE) animal models are invaluable tools used to mimic the complex autoimmune disease in laboratory settings, enabling researchers to investigate the underlying mechanisms, genetic predispositions, and immunological responses associated with SLE. These models, which include spontaneous varieties like NZB/W F1 and MRL/lpr mice, as well as induced models such as pristane-induced lupus, allow for the study of disease initiation, progression, and organ-specific manifestations, thereby facilitating the development of novel therapeutic strategies and enhancing our understanding of SLE pathogenesis.
Fig.1 The construction of humanized systemic lupus erythematosus (SLE) mouse model. (Chen J., et al., 2022)
Spontaneous Models of Systemic Lupus Erythematosus (SLE)
NZB/W F1 Mice
This is the oldest classical model of lupus, generated by crossing New Zealand Black (NZB) and New Zealand White (NZW) strains. These mice develop severe lupus-like phenotypes, including lymphadenopathy, splenomegaly, elevated serum antinuclear autoantibodies, and immune complex-mediated glomerulonephritis. The disease onset and progression are similar to those seen in human SLE patients.
MRL/lpr Mice
This strain develops a severe SLE-like disease characterized by lymphadenopathy, elevated levels of circulating immunoglobulins, and autoantibodies such as anti-dsDNA and rheumatoid factors. The disease is due to a recessive autosomal mutation in the Fas receptor, leading to defective apoptosis.
BXSB/Yaa Mice
These mice develop a lupus-like disease with earlier onset and more severe symptoms in males. The Y-linked autoimmune accelerator (Yaa) mutation involves a translocation of genes from the X chromosome, including TLR7, which contributes to the disease severity.
Our Services
Protheragen's expertise in SLE animal model development ensures that our clients have access to the most advanced and relevant models for their research. Our commitment to scientific excellence and regulatory compliance makes us a trusted partner in the development of novel therapies for SLE.
Induced Models
Pristane-Induced Model
Mechanism: Pristane, a medium-chain alkane, functions similarly to an adjuvant, triggering inflammation and augmenting immune responses. Upon intraperitoneal injection into mice, pristane droplets are engulfed by mononuclear phagocytes, leading to the proliferation and aggregation of T and B lymphocytes, which form granulomas. This process results in the heightened activation of T cells and increased reactivity of B cells, culminating in the production of a wide array of autoantibodies. Additionally, pristane has been shown to induce apoptosis via mitochondrial damage pathways, releasing nuclear antigens that initiate autoimmune reactions.
Method: Protheragen employs a single intraperitoneal injection of 0.5 ml pristane into 6- to 8-week-old female BALB/c (or C57BL/6) mice, which are more susceptible to developing lupus-like lesions compared to males. Mice are monitored monthly for survival, weight, and proteinuria, with blood samples collected biweekly before and after injection to measure autoantibodies such as anti-dsDNA, anti-smRNP, and anti-ribosomal P0. This method provides a reliable and cost-effective model for studying SLE, closely mimicking the clinical manifestations of the disease.
Activated Lymphocyte and Chromatin-Induced Model
Mechanism: This model involves using activated lymphocytes from inbred mice as antigens to immunize syngeneic mice. This process induces the host to produce autoantibodies such as anti-dsDNA and anti-nuclear antibodies. The deposition of antigen-antibody complexes in renal tissue leads to immune complex glomerulonephritis, closely resembling human lupus nephritis.
Method: Protheragen activates splenic lymphocytes from BALB/c mice using ConA and extracts chromatin according to the modified Chiu method. Active chromatin (100 μg in 0.2 ml) is then injected intradermally at the base of the tail and back of BALB/c mice on days 0, 14, 21, and 28. Blood samples are collected from the retro-orbital plexus after the final immunization, and serum is separated for analysis. This method provides a reliable and effective model for studying lupus nephritis, closely mimicking the pathogenesis observed in human SLE.
Humanized Models
Humanized SLE Mouse Models: Our humanized SLE mouse models are designed to better simulate the human disease, offering a more clinically relevant platform for your research. We can engraft human peripheral blood mononuclear cells (PBMCs) or hematopoietic stem cells (HSCs) into immunodeficient mice to partially reconstitute the human immune system. This allows for the study of human immune responses in a living organism, providing invaluable insights into SLE and potential therapeutic interventions.
Genetically Modified Models
We utilize targeted genetic alterations to create and provide models that are essential for elucidating the roles of specific genes in lupus pathogenesis. Our capabilities include developing knockout models lacking key genes (e.g., Fas, BAFF, or TLR7) or models that overexpress relevant genes (e.g., BAFF). These models are critical for understanding the molecular mechanisms driving SLE.
| Model Types | Knockout Mice |
| Model Name | Csf2-KO Mice |
| Also Known As | C57BL/6-Csf2em2 |
| Detailed Description | The Csf2 knockout mice were generated by deleting Exons 1-3 of the Csf2 gene. Homozygous mice with targeted null mutations display lung abnormalities characterized by lymphocytic infiltration and accumulation of surfactant lipids. Additionally, the litter sizes from homozygous breeding pairs are smaller at weaning, primarily due to perinatal mortality (Note from MGI). |
| NCBI ID | 12981 |
| MGI ID | 1339752 |
| Gene Alias | CSF, Csfgm, GMCSF, Gm-CSf, MGI-IGM |
| Sales Status | Sperm cryopreservation |
| Applications & Therapeutic Areas | Growth factors; NF-KB pathway; Allergy and asthma |
| Ensembl ID | ENSMUSG00000018916 |
| Pubmed | CSF2 |
| Human Ortholog | CSF2 |
Case Study
Chronic Graft-versus-Host Disease (cGVHD)-SLE Mouse Model
This model is based on the transplantation of mouse splenocytes, which leads to an irreversible autoimmune attack on the mouse's own tissues, manifesting symptoms similar to SLE and cGVHD over several weeks to months. Mice in this model typically exhibit reduced appetite, weight loss, liver dysfunction, and hepatosplenomegaly, closely resembling the clinical presentation of cGVHD. They also display typical SLE symptoms, such as lymphocyte proliferation in the spleen, production of antinuclear antibodies, leukopenia and anemia, and renal dysfunction. This model is widely used for studying the mechanisms of SLE and for developing and optimizing therapeutic approaches.
Fig 2. Spleen and anti-dsDNA level.
Protheragen offers platforms for preclinical testing of novel therapies. Our models ensure that treatments are effective in a controlled and relevant environment before advancing to clinical trials. This reduces the risk of failure in later stages and accelerates the development of new therapies. If you are interested in our services, please feel free to contact us.
References
- Chen, Jiaxuan, et al. "Humanized mouse models of systemic lupus erythematosus: opportunities and challenges." Frontiers in Immunology 12 (2022): 816956.
- Pathak, Simanta, and Chandra Mohan. "Cellular and molecular pathogenesis of systemic lupus erythematosus: lessons from animal models." Arthritis research & therapy 13.5 (2011): 241.
- Rottman, J. B., and C. R. Willis. "Mouse models of systemic lupus erythematosus reveal a complex pathogenesis." Veterinary pathology 47.4 (2010): 664-676.