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Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by severe itching, redness, and recurrent eczema, significantly impairing the quality of life for millions worldwide. Despite its prevalence, current treatments often fall short, particularly for moderate-to-severe cases, highlighting the need for advanced therapeutic options.
Immune dysregulation plays a key role in AD pathogenesis, primarily through type 2 inflammation, characterized by elevated Th2 cytokines such as IL-4, IL-13, and IL-31 (Facheris et al., 2023). IL-4 and IL-13, signaling via the IL-4 receptor (IL-4R), drive inflammation and skin barrier dysfunction. Additionally, thymic stromal lymphopoietin (TSLP), released by epithelial cells in response to allergens and microbes, acts through its receptor (TSLPR) to amplify type 2 immune responses, contributing to chronic itching and inflammation (Nakajima et al., 2020).
Immune pathways in AD. (Source: Salimian et al., 2022)
At Biocytogen, we provide AD disease models using both wild-type and drug-targeted humanized mice, which carry human genes for key AD-related pathways such as IL-4/IL-4R (B-hIL4/hIL4RA mice) and TSLP/TSLPR (B-hTSLP/hTSLPR mice). These models offer a versatile and reliable platform for preclinical drug testing, enabling the evaluation of therapeutic efficacy in both standard and human-relevant systems.
Case Study: OXA-Induced AD Model Using B-hTSLP/hTSLPR Mice
Biocytogen’s OXA-Induced AD Mouse Model sensitizes mice with oxazolone (OXA) to replicate key features of human AD, such as inflammation and skin barrier dysfunction. Known for its well-characterized immune response and high reproducibility, this model offers drug developers a reliable and efficient platform to evaluate therapeutic efficacy and accelerate the translation of innovative treatments from bench to bedside.
Efficacy validation of tezepelumab (human TSLP antibody, in house) in an OXA-induced AD model using B-hTSLP/hTSLPR mice. (A) Body weight change. (B) Ear thickness. (C) Serum total IgE. (D) Total score. (E) Epidermal thickness. (F) Eosinophil infiltration score. Dexamethasone: Corticosteroid for inflammation. Tezepelumab: Human monoclonal antibody targeting TSLP. (A–B: Two-way ANOVA; C–F: One-way ANOVA; *p < 0.05, **p < 0.01, ****p < 0.0001).
Case Study: MC903-Induced AD Mouse Model Using BALB/c Mice
Biocytogen’s MC903-Induced AD Mouse Model utilizes MC903, a vitamin D3 analog, to induce AD-like symptoms. This model closely mimics human AD pathophysiology, offering a reliable and reproducible platform for efficacy testing and drug development.
Dexamethasone and Crisaborole (a PDE-4 inhibitor) improve MC903-induced atopic dermatitis in BALB/c mice. (A) Body weight change. (B) Ear thickness change. (C) Total IgE levels in serum. (D) Epidermal thickness score. (E) Eosinophil infiltration score. (F) Histology score. (A–C: one-way ANOVA; **p < 0.01, ****p < 0.0001).
AD-Related Humanized Mouse Models at Biocytogen
Ready to explore how Biocytogen’s AD models can support your research? Contact us today to discuss how our models can advance your drug development pipeline!
Reference
Facheris, Paola, et al. "The translational revolution in atopic dermatitis: the paradigm shift from pathogenesis to treatment." Cellular & molecular immunology 20.5 (2023): 448-474.
Nakajima, Saeko, et al. "Anti-TSLP antibodies: Targeting a master regulator of type 2 immune responses." Allergology International 69.2 (2020): 197-203.
Salimian, Jafar, et al. "Atopic dermatitis: molecular, cellular, and clinical aspects." Molecular Biology Reports 49.4 (2022): 3333-3348.