Background/Purpose: Psoriatic arthritis (PsA), a complex inflammatory disorder that affects up to 30% of psoriasis patients. It is marked by clinical heterogeneity and a lack of standardized diagnostic criteria, posing significant challenges in therapeutic development. Despite advancements in targeted therapies, gaps in understanding disease pathogenesis and variable clinical phenotypes highlight the need for robust, translational preclinical models. Here, we established two inducible PsA mouse models to support preclinical drug efficacy testing and accelerate therapeutic discovery.

Methods: Two distinct PsA models were developed: 1. Mannan-induced PsA model, female BALB/c mice (12-13 weeks) received intraperitoneal mannan injections (every 4 days) combined with a single subcutaneous Complete Freund’s Adjuvant (CFA) injection into the hind paw. On day 12, ear and paw tissues were analyzed for histopathology (HE staining, inflammation scoring), qPCR (inflammatory cytokines: Ifng, Il6, Il17a, Tnf, Il23), and serum cytokines (CBA assay: IL-12, IFN-γ, IL-6). 2. AAV-hIL23-induced PsA model, female NOD ShiLtj mice (8 weeks) were injected intravenously with 1×10¹² particles/mL AAV-hIL23. Serum hIL-23 levels were monitored weekly (ELISA), and tissues were analyzed at day 35 for histopathology and cytokine expression. Pharmacodynamic evaluation in the mannan-induced PsA model: Treatment arms included dexamethasone (1 mg/kg, daily oral) and upadacitinib (20 mg/kg, BID oral). In as separate study, PsA was induced with mannan in BALB/c-hIL23AhIL12B mice (GemPharmatech), followed by subcutaneous injection with risankizumab (10 mg/kg, BIW). Disease progression was monitored via psoriasis/arthritis scoring of the ears and hind limbs.

Results: Mannan-induced model, PsA mice exhibited marked ear erythema, paw/ankle swelling, elevated psoriasis/arthritis scores, as well as elevated expression of inflammatory cytokines (Ifng, Il6, Il17a, Tnf, Il23), and increased serum IL-12, IFN-γ, and IL-6. Histopathology revealed epidermal hyperplasia, inflammatory infiltration, and bone erosion. Both dexamethasone and upadacitinib reduced skin/joint inflammation and disease scores. Risankizumab effectively suppressed skin/joint pathology and disease scores in mannan-induced BALB/c-hIL23AhIL12B mice PsA model. In AAV-hIL23 model, sustained hIL-23 expression (serum, days 14–35) drove progressive skin thickening, elevated psoriasis scores, and arthritis-associated swelling, with upregulated Il6, Il17a, Il22, and Tnf.

Conclusion: We validated two inducible PsA models that reproduce key clinical features of human PsA. The mannan-induced model enables the evaluation of small molecules (e.g., JAK inhibitors) and biologics in humanized strains, while the AAV-hIL23 model may provide a platform for IL-23 pathway-targeted therapies. Together, these models help address critical gaps in the preclinical PsA drug development process.

« Back to ACR Convergence 2025

ACR Meeting Abstracts - https://acrabstracts.org/abstract/application-of-psoriatic-arthritis-mouse-models-in-preclinical-pharmacodynamic-evaluation/