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Scratch Migration Assay and Dorsal Skinfold Chamber for In Vitro and In Vivo Analysis of Wound Healing
Published on: September 26, 2019
Disease-linked connexin26 S17F promotes volar skin abnormalities and mild wound healing defects in mice
Eric Press1, Katanya C Alaga2, Kevin Barr2
1Department of Physiology and Pharmacology, University of Western Ontario, London, ON, Canada.
Abstract:
Several mutant mice have been generated to model connexin (Cx)-linked skin diseases; however, the role of connexins in skin maintenance and during wound healing remains to be fully elucidated. Here we generated a novel, viable, and fertile mouse (Cx26CK14-S17F/+) with the keratitis-ichthyosis-deafness mutant (Cx26S17F) driven by the cytokeratin 14 promoter. This mutant mouse mirrors several Cx26-linked human skin pathologies suggesting that the etiology of Cx26-linked skin disease indeed stems from epidermal expression of the Cx26 mutant. Cx26CK14-S17F/+ foot pad epidermis formed severe palmoplantar keratoderma, which expressed elevated levels of Cx26 and filaggrin. Primary keratinocytes isolated from Cx26CK14-S17F/+ neonates exhibited reduced gap junctional intercellular communication and migration. Furthermore, Cx26CK14-S17F/+ mouse skin wound closure was normal but repaired epidermis appeared hyperplastic with elevated expression of cytokeratin 6. Taken together, we suggest that the Cx26S17F mutant disturbs keratinocyte differentiation and epidermal remodeling following wound closure. We further posit that Cx26 contributes to epidermal homeostasis by regulating keratinocyte differentiation, and that mice harboring a disease-linked Cx26 mutant display epidermal abnormalities yet retain most wound healing properties.
Insights
Connexin 26 (Cx26) mutations cause skin diseases. This study shows Cx26 mutants disrupt keratinocyte differentiation and skin repair, impacting epidermal homeostasis.
Area of Science:
- Dermatology
- Cell Biology
- Genetics
Background:
- Connexins (Cx) are crucial for skin maintenance and wound healing.
- Mutant Cx-linked skin diseases are modeled in mice, but their precise roles require further study.
Purpose of the Study:
- To investigate the role of connexin 26 (Cx26) in skin homeostasis and wound healing using a novel mouse model.
- To determine if epidermal expression of a Cx26 mutation causes skin pathologies.
Main Methods:
- Generated a novel Cx26 mutant mouse (Cx26CK14-S17F/+) driven by the cytokeratin 14 promoter.
- Analyzed skin phenotype, keratinocyte function (gap junction communication, migration), and wound healing in mutant mice.
- Assessed expression of Cx26, filaggrin, and cytokeratin 6 in mutant skin.
Main Results:
- The Cx26CK14-S17F/+ mouse model exhibited palmoplantar keratoderma with elevated Cx26 and filaggrin.
- Primary keratinocytes showed reduced gap junctional communication and migration.
- Wound closure was normal, but repaired epidermis was hyperplastic with increased cytokeratin 6 expression.
Conclusions:
- Epidermal expression of the Cx26S17F mutant causes skin pathologies, mirroring human Cx26-linked diseases.
- Cx26S17F mutant disrupts keratinocyte differentiation and epidermal remodeling post-wound healing.
- Cx26 is vital for epidermal homeostasis, regulating keratinocyte differentiation; disease-linked mutants cause abnormalities but largely preserve wound healing.
