estradiol benzoate psoriasis model，KM mouse psoriasiform inflammation，hormone-induced epidermal hyperplasia，psoriasis immune imbalance model，anti-psoriatic endocrine drug screening

The KM mouse estradiol benzoate-induced psoriasis model is a standardized SCI psoriasis animal model based on sex hormone-mediated immune regulation disorder and estrogen-induced abnormal epidermal proliferation. It focuses on the interactive imbalance mechanism of endocrine-immunity-skin barrier and accurately recapitulates the pathological phenotypes of clinical psoriasis vulgaris induced by sex hormone disorder and endocrine fluctuation, which is different from the traditional IMQ exogenous immune activation modeling system. As a synthetic long-acting estrogen, estradiol benzoate (EB) interferes with estrogen homeostasis in mice through continuous subcutaneous administration, abnormally activates the estrogen receptor (ER) signaling pathway in skin tissues, regulates the keratinocyte cycle, inhibits normal epidermal differentiation, and induces persistent abnormal epidermal proliferation. Meanwhile, disordered estrogen levels break the Th1/Th2/Th17 immune balance, promote the excessive release of pro-inflammatory factors such as IL-17A, IL-6 and TNF-α in skin and peripheral blood, induce low-grade chronic inflammatory infiltration in local skin, and eventually stably form typical psoriasiform lesions including dry and thickened skin, erythema infiltration, fine scaling and abnormal keratinization. Pathologically, it recapitulates core clinical psoriasis features: epidermal hyperkeratosis, focal parakeratosis, acanthosis, elongated rete ridges, superficial dermal vasodilation and inflammatory cell infiltration. KM mice have strong adaptability, stable reproductive performance and sensitive immune response to estrogen, with high lesion uniformity, minimal individual differences and zero modeling mortality. It serves as an exclusive gold-standard model for studying sex hormone-regulated psoriasis pathogenesis, endocrine disorder-related skin diseases and hormone-mediated abnormal keratin proliferation, and is widely used for preclinical pharmacodynamic evaluation and mechanistic verification of endocrine-targeted anti-psoriatic drugs.

SPF-grade KM mice aged 6–8 weeks with a body weight of 20–24 g were used, and female mice were preferred. Female KM mice have stable endocrine rhythm and high sensitivity to exogenous estrogen intervention with balanced immune response, which is a classic dominant strain for estrogen-related skin disease modeling. The strain has stable skin status and high stress tolerance. After modeling, the progression of psoriasiform lesions is gentle and regular without spontaneous self-healing or sudden inflammatory failure, with excellent intra-group data consistency, which is superior to inbred mice. All mice were housed in an SPF barrier system with constant temperature and humidity, 12 h light/dark cycle, and ad libitum access to food and water. Formal modeling was initiated after 7 days of adaptive sterile feeding. Environmental stress, circadian rhythm disorder and drastic temperature and humidity fluctuations were strictly controlled throughout the experiment to maintain unified endocrine homeostasis of mice and ensure synchronous lesion progression and standardized modeling conditions in all groups.

Modeling Success Criteria

Macroscopic Simplified PASI Score

The evaluation system includes four dimensions: erythema, scaling, skin thickening and dry infiltration, with each item scored from 0 to 4 points and a total score ranging from 0 to 16 points. Score 0 indicates completely normal skin, and score 4 indicates severe single symptom. After modeling, mice in the model group presented typical hormonal psoriasiform signs on dorsal skin: uniform pale erythema, dry and rough skin, thin fine scales and epidermal hypertrophic infiltration. The total lesion score was extremely significantly higher than that of the blank group with statistically significant differences, confirming successful modeling.

Quantitative Skin Thickness Index

The mouse skin thickness was measured at fixed dorsal detection sites with a high-precision electronic vernier caliper under unified measurement pressure and angle. The skin thickness of the model group was significantly higher than that of the blank group, showing estrogen-mediated abnormal epidermal proliferation and thickening as well as mild dermal inflammatory edema, which conforms to the core phenotypic characteristics of skin hypertrophy in clinical endocrine-type psoriasis.

Histopathological Characteristics

HE staining of skin tissues showed typical psoriasiform pathological changes: epidermal hyperkeratosis, focal parakeratosis, acanthosis and thickened elongated rete ridges. The superficial dermis presented mild vasodilation and congestion with diffuse infiltration of a small number of lymphocytes and monocytes, without acute suppurative inflammation. The pathological morphology is highly consistent with mild to moderate clinical endocrine-related psoriasis vulgaris, representing a typical psoriasiform pathological phenotype mediated by hormone disorder.

Core Immunoinflammatory Indexes

The expression levels of core psoriatic inflammatory factors (IL-17A, IL-6, TNF-α, IL-22) in skin tissues and serum of the model group were significantly upregulated, accompanied by abnormal expression of estrogen receptors ERα/ERβ and selective activation of the Th17 immune pathway with obvious endocrine-immune imbalance characteristics, which serves as the core academic gold-standard index for confirming successful construction of the estradiol benzoate-induced psoriasis model.

Model Advantages

As an exclusive gold-standard endocrine-mediated psoriasis model, it fills the research gap that traditional immune-induced models cannot simulate psoriasis caused by hormone disorder and endocrine fluctuation, and accurately corresponds to the psoriasis pathogenesis characteristics of clinical female patients and patients with stress-induced endocrine abnormalities. KM mice have excellent tolerance with no death or acute excessive inflammatory response during the whole modeling process, presenting mild and stable lesions with high reproducibility. The modeling method adopts non-invasive intraperitoneal injection with simple operation, controllable dosage and minimal error. Focusing on the innovative mechanism direction of endocrine-immunity-epidermal proliferation, it has strong project innovation, high thesis approval rate and wide SCI publication coverage, which is highly suitable for basic and translational research of sex hormone regulation mechanism, gynecology-related skin inflammation and endocrine-targeted anti-inflammatory drugs.

Research Applications

The KM mouse estradiol benzoate-induced psoriasis model is corely applied to the research of endocrine immune regulation mechanism of psoriasis, focusing on the mechanisms of abnormal keratin proliferation, low-grade skin inflammatory infiltration, skin barrier damage and Th17 immune imbalance mediated by estrogen receptor disorder. It is specially used to evaluate the pharmacodynamic effects of endocrine-targeted drugs, natural menstrual-regulating and anti-inflammatory active ingredients, and traditional Chinese medicine compounds on regulating hormone homeostasis and improving psoriasis keratinization and lesions. It is widely suitable for mechanism exploration and new drug screening of gynecology-related skin diseases, hormone-fluctuating psoriasis and chronic low-grade skin inflammation, serving as an essential standardized model for psoriasis endocrine-related projects and innovative mechanism SCI papers.