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Establishment of a Mouse Model for Porokeratosis Due to Mevalonate Diphosphate Decarboxylase Deficiency
Kexin Peng1, Wenghong Wong1, Qiaoan Zhang1
1Department of Dermatology, Huashan Hospital, Shanghai Institute of Dermatology, Fudan University, Shanghai, China.
Introduction:
Porokeratosis (PK) is an autoinflammatory keratinization disease (AIKD) characterized by circular or annular skin lesions with a hyperkeratotic rim, pathologically shown as the cornoid lamella. Four genes that cause PK are associated with the mevalonate (MV) pathway. In Chinese PK patients, mevalonate diphosphate decarboxylase (MVD) is the most common causative gene. The lack of an animal model has greatly limited research on PK pathogenesis.
Materials And Methods:
In this research, we constructed K14-CreERT2-Mvdfl/fl mice using the Cre-LoxP system to create a mouse model for in-depth studies of PK. The Epidermal Mvd gene was knocked out by intraperitoneal injection of Tamoxifen (TAM). Pathology, immunohistochemistry, RNA-seq, and Western Blot analysis were performed.
Results:
Skin lesions appeared following Mvd deficiency, and pathological examination revealed the characteristic cornoid lamella, as well as cutaneous inflammation. Furthermore, we observed elevated levels of IL-17A and IL-1β, and a decreased Loricrin level in epidermal Mvd-deficient mice. Compared with the wild-type (WT) group, Mvd deficiency activated the expression of lipid metabolism-related proteins.
Conclusion:
We developed the first mouse model for PK research, enabling further studies on disease development and treatment approaches.
Insights
Researchers developed the first mouse model for porokeratosis (PK) by knocking out the mevalonate diphosphate decarboxylase (MVD) gene. This model exhibits characteristic PK skin lesions and inflammation, aiding future research into this autoinflammatory keratinization disease.
Area of Science:
- Dermatology
- Genetics
- Molecular Biology
Background:
- Porokeratosis (PK) is an autoinflammatory keratinization disease (AIKD) characterized by distinctive skin lesions.
- Four genes linked to PK are associated with the mevalonate (MV) pathway, with MVD being the most common in Chinese patients.
- Limited research on PK pathogenesis is attributed to the lack of a suitable animal model.
Purpose of the Study:
- To develop the first mouse model for studying porokeratosis.
- To investigate the role of mevalonate diphosphate decarboxylase (MVD) in PK pathogenesis.
- To provide a platform for future PK research and therapeutic development.
Main Methods:
- Construction of K14-CreERT2-Mvdfl/fl mice using the Cre-LoxP system.
- Intraperitoneal injection of Tamoxifen (TAM) to induce epidermal Mvd gene knockout.
- Analysis included pathology, immunohistochemistry, RNA-seq, and Western Blot.
Main Results:
- Mvd deficiency in mice led to the development of skin lesions with characteristic cornoid lamella and cutaneous inflammation.
- Elevated levels of IL-17A and IL-1β, and decreased Loricrin were observed.
- MVD deficiency activated lipid metabolism-related protein expression.
Conclusions:
- The successful development of the first Mvd-deficient mouse model for PK.
- This model facilitates in-depth studies of PK pathogenesis.
- Enables exploration of novel treatment strategies for porokeratosis.
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