Modeling Principle

The DBA1 Mouse Mannan Psoriatic Arthritis Model is a classic SCI gold-standard comorbid animal model for the pathological mechanism analysis of psoriatic arthritis (PsA), immune regulation of skin-joint comorbidity, research on the IL-23/IL-17 inflammatory axis, and preclinical efficacy evaluation of novel anti-PsA drugs. Relying on the natural genetic susceptibility of DBA1 mice and their high sensitivity to mannan immune stimulation, the model specifically breaks immune tolerance in skin and joint tissues through repeated intraperitoneal injection of yeast-derived mannan, systematically activates Th17 cell-mediated autoimmune inflammatory pathways, and accurately recapitulates the typical clinical comorbid phenotypes of human psoriatic arthritis, including cutaneous scaling and erythema, symmetrical toe arthritis, sausage-like digit lesions, and progressive articular bone damage. As a potent pattern recognition receptor agonist, mannan can continuously activate the innate immune response, induce abnormal proliferation of skin stratum corneum, inflammatory cell infiltration and epidermal thickening with scaling, and simultaneously trigger persistent synovitis, pannus hyperplasia, cartilage erosion and bone resorption in distal interphalangeal and metatarsophalangeal joints of limbs, completely reproducing the full-temporal pathological process of clinical PsA characterized by initial skin lesions, secondary joint inflammation and chronic progressive bone destruction. Compared with imiquimod-induced single psoriasis skin models and collagen-induced single arthritis models, this model has core advantages of synchronous formation of dual skin-joint lesions, highly clinical-consistent PsA pathological phenotypes, nearly 100% modeling rate, stable inflammatory timeline and extremely low individual data dispersion. It is currently recognized as the most clinically consistent composite animal model for psoriatic arthritis. The experimental paradigm fully complies with the specifications of high-impact SCI journals in rheumatology, dermatology and osteoarticular translational medicine, and can be directly applied to National Natural Science Foundation projects, postgraduate research proposals and dissertations, serving as a standardized mainstream model for basic mechanism verification and novel targeted drug screening of psoriatic arthritis.

Modeling Success Criteria

Quantitative Skin and Joint Clinical Phenotype Criteria

Unified model evaluation is completed at the inflammatory peak of 28 d after modeling, and there are significant statistical differences between the model group, blank group and vehicle control group: 1. Skin phenotype: symmetrical erythema, epidermal thickening, dry scaling and invasive uplift appear on the auricular and paw skin of mice, consistent with typical psoriatic lesion characteristics, and the PASI score is significantly higher than that of the control groups; 2. Joint phenotype: symmetrical redness, swelling and bulging occur in distal limb toe and metatarsophalangeal joints with characteristic sausage-like dactylitis and mild limited limb movement, without unilateral occasional lesions; 3. Behavioral performance: mice show slightly decreased activity, uneven limb weight bearing and abnormal grooming behavior, without obvious lethargy or eating disorders; 4. Quantitative criteria: the skin PASI score, joint inflammation score and limb swelling degree of the model group are significantly higher than those of the control groups with statistically significant inter-group differences, while there is no significant difference between the vehicle control group and blank group, eliminating solvent and puncture interference; 5. Disease course stability: skin lesions and joint inflammation progress continuously without spontaneous remission or invalid model individuals, with stable and homogeneous inflammatory phenotypes. The DBA1 mouse mannan-induced psoriatic arthritis model is successfully established when all the above dual skin-joint phenotypic indicators reach the standard.

Histomorphometric Gold-Standard Indexes

Gold-standard histopathological evaluation of skin and joint tissues: the model group presents typical psoriatic pathological changes in skin tissues, including epidermal acanthosis, hyperkeratosis, parakeratosis, Munro microabscess formation, and massive infiltration of lymphocytes and neutrophils in the dermis; synovial tissue shows significant proliferation and thickening, disordered layers and continuous massive inflammatory cell infiltration with increased intra-articular inflammatory exudation, and synovial angiogenesis and pannus invade the joint space; articular cartilage matrix is lost with thinning and disordered arrangement of cartilage layer and degenerative damage, and cortical bone presents PsA-characteristic osseous damage such as bone resorption and trabecular disorder. The blank group and vehicle control group have complete skin structure, clear epidermal layers without keratosis abnormality or inflammatory infiltration, and intact synovial, cartilage and bone tissues. Core histomorphometric indexes: the epidermal thickening rate, skin inflammatory infiltration area, synovial hyperplasia thickness, joint inflammatory infiltration grade, cartilage damage score and bone erosion degree of the model group are significantly higher than those of the control groups. The pathological phenotype is completely consistent with the clinical skin-joint comorbidity characteristics of psoriatic arthritis, meeting the SCI gold standard for academic credibility.

Academic Evidence for Model Validity

The core academic validity basis of this model is as follows: relying on the genetic susceptibility background of DBA1 mice, mannan specifically activates the classic IL-23/IL-17/Th17 core inflammatory axis of psoriatic arthritis, breaks immune tolerance in skin and joint tissues, synchronously induces abnormal keratin proliferation inflammation in skin and inflammatory damage of distal joint synovium, and accurately recapitulates the characteristic pathological mechanism of clinical PsA: psoriatic skin lesions-symmetrical dactylitis-sausage-like digit lesions-progressive osteochondral destruction. This model has a clear modeling mechanism, stable lesion timeline, synchronous formation of dual skin-joint phenotypes and industry-recognized excellent experimental reproducibility, which can accurately quantify and evaluate the regulatory and repair efficacy of various interventions on psoriatic skin lesions, joint inflammation, osteochondral damage and Th17 immune disorders, serving as an authoritative SCI gold-standard model for comorbidity mechanism research of psoriatic arthritis and preclinical screening of anti-PsA targeted drugs.

Model Advantages

The DBA1 Mouse Mannan Psoriatic Arthritis Model is a high-impact SCI mainstream gold-standard model in the fields of psoriatic skin-joint comorbidity mechanism, IL-23/IL-17 inflammatory axis regulation, Th17 immune disorder, PsA bone destruction mechanism and preclinical evaluation of novel anti-psoriatic arthritis drugs. Relying on the unique genetic susceptibility of DBA1 mice, it can synchronously and spontaneously form dual lesions of psoriatic skin and distal dactylitis, perfectly recapitulating the clinical comorbidity characteristics of PsA and superior to single skin or single joint models. The model adopts non-invasive intraperitoneal injection with simple operation, controllable cycle, moderate cost, extremely low animal mortality and low ethical risks. It achieves a modeling rate of 98%–100% with highly homogeneous lesion phenotypes, minimal individual differences, clear inflammatory sequence, stable peak value and industry-leading data reproducibility. It precisely targets the core IL-23/IL-17/Th17 pathogenic pathway of PsA with highly clinically consistent pathological mechanisms. It adapts to multi-dimensional closed-loop verification including skin appearance, joint function, histopathology, bone microstructure and molecular pathways. The experimental data is highly recognized and easily accepted by authoritative SCI journals in dermatology, rheumatology and translational medicine, fully adapting to the high-level scientific research system of National Natural Science Foundation projects, fund application, research proposals and postgraduate dissertations.

Research Applications

This model is mainly used to systematically elucidate the core molecular mechanisms of mannan-mediated IL-23/IL-17 axis activation, Th17 immune imbalance, abnormal skin keratin proliferation, distal joint inflammatory damage and PsA osteochondral erosion. It accurately evaluates the dual protective and immune regulatory efficacy of traditional Chinese medicine compounds, natural active ingredients, chemically synthesized drugs, targeted preparations and biomaterials on psoriatic skin damage, joint inflammation and bone destruction. It verifies the linked pathogenic mechanism of skin immune disorder-distal joint inflammation-bone metabolism imbalance and explores novel immune intervention targets and signaling pathways for psoriatic arthritis, optimizing the collaborative intervention scheme for early PsA skin lesions and joint inflammation. It is widely applied in full scientific research scenarios including basic mechanism research of psoriatic arthritis, preclinical efficacy screening of new anti-PsA drugs, translational medicine research of skin-rheumatic comorbidity, fund project application, research proposal writing and high-impact SCI paper publication, serving as the most clinically consistent standardized SCI gold-standard comorbidity model in the current PsA research field.

DBA1 mouse, mannan-induced psoriatic arthritis, PsA animal model, skin scaling, dactylitis, sausage-like digit, IL-23/IL-17 inflammatory axis, psoriatic