A Mouse Model for Conditional Expression of Activated β-Catenin in Epidermal Keratinocytes

Authors

Vineet K Maurya
Yan Ying
John P Lydon

Publication Date

10-1-2024

Journal

Transgenic Research

DOI

10.1007/s11248-024-00402-z

PMID

39110314

PMCID

PMC11588969

PubMedCentral® Posted Date

8-7-2024

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

Animals, beta Catenin, Keratinocytes, Mice, Doxycycline, Epidermis, Mice, Transgenic, Cell Proliferation, Hair Follicle, Keratin-5, Female

Abstract

We report the generation and characterization of the K5: CAT bigenic mouse in which the constitutively activated form of β-catenin (ΔN89 β-catenin) is conditionally expressed in cytokeratin-5 (K5) positive epidermal keratinocytes. Following short-term doxycycline intake during the telogen resting phase, the adult K5: CAT bigenic develops enlarged pilosebaceous units that expand deep into the dermis, an expansion usually observed during the anagen growth phase. Prolonged doxycycline treatment results in significant thickening and folding of the K5: CAT epidermis. During this persistent induction period, there is clear evidence of increased keratinocyte proliferation, particularly in the epidermal basal cell layer and the outer root sheath of the hair follicle. This unscheduled increase in cellular proliferation likely explains the decrease in hair density observed in the K5: CAT mouse following persistent doxycycline intake. Numerous hyperplastic endometrioid cysts, which display cornification toward their lumens, are also observed during this treatment period. Remarkably, de-induction of ΔN89 β-catenin expression through doxycycline withdrawal results in a marked reversal of the skin phenotype, suggesting that these morphological changes are dependent on continued signaling by β-catenin and/or its downstream molecular mediators. Joining a small group of mouse models for conditional β-catenin signaling, our K5: CAT mouse model will be particularly useful in identifying those molecular mediators of β-catenin that are responsible for initiating and maintaining these phenotypic responses in the K5: CAT skin. Such studies are predicted to shed more light on β-catenin signaling in epidermal epithelial morphogenesis, hair follicle cycling, and hair growth pathologies.