Inflammation and Autoimmunity

Atopic Dermatitis

Biocytogen uses wild-type C57BL/6 mice and target humanized mice to experimentally induce AD-like lesions via oxazolone (OXA) sensitization and continuous challenge or application of MC903. The resulting atopic dermatitis mouse models can be used for preclinical efficacy evaluation of therapeutic candidates.

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  • Introduction
  • Results

Publication

    Introduction

    Atopic dermatitis (AD) is a chronic skin disease that presents with itching, erythema and squamous lesions, and can be associated with cardiovascular disease, mental disorders (depression, anxiety, sleep disorders, etc.) and other diseases.

    Atopic dermatitis mouse models:

    • Induced by enhanced skin sensitization using epithelial sensitive antigens, haptens, etc.
    • Genetically engineered atopic dermatitis mouse model;
    • Spontaneous atopic dermatitis mouse model.

    Biocytogen uses wild-type C57BL/6 mice and B-hIL4/hIL4RA double humanized mice on the C57BL/6 background to experimentally induce AD-like lesions via oxazolone (OXA) sensitization and continuous challenge or application of MC903. The resulting atopic dermatitis mouse models can be used for preclinical efficacy evaluation of therapeutic candidates.

    Results
    Oxazolone induced AD model
    Establishment of OXA induced AD Mouse Model
    • Experimental Animals: C57BL/6, BALB/c, B-hIL4/hIL4RA, B-hTSLP/hTSLPR, 7-8 weeks old, femal
    • Modeling reagent: Oxazolone (OXA)
    • Modeling sites: Right ear and dorsal skin
    • Modeling method: Topically applicated on dorsal and ear. Sensitization: day 0; Challenge: day 7-25
    Readouts
    Included tests Clinical scores Ear thickness
    Ear histopathology (H&E) Immune infiltration
    Epidermal thickness
    Histology scores
    Optional tests Molecular levels Serum total IgE
    Protein level (Elisa or Luminex)
    Establishment of OXA-induced AD Model of C57BL/6 Mice

    Establishment of AD model of C57BL/6 mice. A. ear thickness change during treatment. B. Mouse total IgE in serum of each group on Day 6, 13, 20, 26. (A. Two-way ANOVA; B. One-way ANOVA; ** p< 0.01, *** p< 0.001).

    Efficacy Evaluation of Dexamethasone in OXA-induced AD Model of C57BL/6 Mice

    Efficacy evaluation of Dexamethasone in AD model of C57BL/6 mice. A. ear thickness change during treatment. B. Mouse total IgE in serum. C. Eosinophil infiltration score of ear histopathology. (A-B. Two-way ANOVA; C-D. One-way ANOVA; *** p< 0.001, **** p< 0.0001).

    Efficacy Evaluation of Dexamethasone in OXA-induced AD Model of BALB/c Mice

    Efficacy evaluation of Dexamethasone in AD model of BALB/c mice. A. ear thickness change during treatment. B-D. Mouse total IgE in in serum on Day 7, 17, 26. (A. Two-way ANOVA; B-D. One-way ANOVA; *p<0.05, **p<0.01, *** p< 0.001).

    Efficacy Evaluation of Dupilumab in OXA-induced AD Model of B-hIL4/hIL4RA Mice

    Efficacy Validation on B-hIL4/hIL4RA AD Models for Dupilumab. A. Body weight change during treatment. B. ear thickness change during treatment. C. Mouse total IgE in serum. D. Eosinophil infiltration score. E. Epidermal thickness. F. Histology score (A-B. Two-way ANOVA; C-F. One-way ANOVA; * p< 0.05, ** p< 0.01, *** p< 0.001).

    Efficacy Evaluation of Dupilumab in OXA-induced AD Model of B-hIL4/hIL4RA Mice

    Protein expression analysis in OXA-induced AD model of B-hIL4/hIL4RA mice by ELISA.
    Ear samples of modeling area were collected on day 9, 16, 26 and 26 and analyzed ELISA. Tissue sample homogenate supernatants were loaded for ELISA detection, and the results were standardized by total protein concentration of the corresponding sample.

    Efficacy Evaluation of Anti-human TSLP in OXA-induced AD Model of B-hTSLP/hTSLPR Mice

    Efficacy Validation on B-hTSLP/hTSLPR AD Models for anti-human TSLP. A. Body weight change during treatment. B. ear thickness change during treatment. C. Mouse total IgE in serum. D. Total score. E. Epidermal thickness. F. Eosinophil infiltration score. (A-B. Two-way ANOVA; C-F. One-way ANOVA; * p< 0.05, ** p< 0.01, **** p< 0.0001).