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Decreased Imiquimod-Induced Psoriasis-Like Skin Inflammation in a Novel MvdF250S/+ Knock-In Mouse Model
Yumeng La1, Wenghong Wong1, Kexin Peng1
1Department of Dermatology, Huashan Hospital, Fudan University, Shanghai Institute of Dermatology, Shanghai, People's Republic of China.
Inflammation
|May 25, 2023
Summary
A new mouse model with a mevalonate-diphosphate decarboxylase (MVD) mutation shows reduced skin inflammation and activated autophagy, offering insights into porokeratosis pathogenesis.
Area of Science:
- Biochemistry
- Genetics
- Dermatology
Background:
- The mevalonate pathway, regulated by mevalonate-diphosphate decarboxylase (MVD), is crucial for synthesizing cholesterol, hormones, and isoprenoids.
- A specific MVD mutation (c.746 T>C) is linked to porokeratosis (PK), an autoinflammatory keratinization disease with poorly understood mechanisms and limited treatment options.
- Currently, there is a lack of suitable animal models to study PK and the role of MVD mutations.
Purpose of the Study:
- To investigate the in vivo function of the MvdF250S/+ mutation, equivalent to a common PK-associated human mutation.
- To develop and characterize a novel MvdF250S/+ mouse model for studying MVD's role in skin inflammation and disease.
Main Methods:
- CRISPR/Cas9 technology was used to create the MvdF250S/+ mouse model.
- Mice were treated with imiquimod (IMQ) to induce skin inflammation.
- Cutaneous proliferation, protein levels of IL-17a and IL-1β, collagen generation, and Fabp3 expression were analyzed.
- Autophagy activation was assessed in the MvdF250S/+ mice.
Main Results:
- The MvdF250S/+ mice exhibited reduced cutaneous Mvd protein expression.
- Upon IMQ induction, these mice showed decreased susceptibility to skin inflammation, characterized by reduced proliferation and lower IL-17a and IL-1β levels compared to wild-type (WT) mice.
- IMQ-induced MvdF250S/+ mice displayed downregulated collagen and upregulated Fabp3, with no significant changes in cholesterol-related genes.
- The MvdF250S/+ mutation was found to activate autophagy.
Conclusions:
- The MvdF250S/+ mouse model provides valuable insights into the biological function of MVD in the skin.
- The findings suggest a role for MVD in regulating skin inflammation and potentially other cellular processes like autophagy, independent of direct cholesterol regulation.
- This model can aid in understanding porokeratosis pathogenesis and exploring therapeutic strategies.
