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Updated: Jun 18, 2026
Flat Mount Imaging of Mouse Skin and Its Application to the Analysis of Hair Follicle Patterning and Sensory Axon Morphology
Published on: June 25, 2014
Mouse model of Merkel cell carcinoma derived from the hair follicle
Madison Weber1, Amanda Ackermann1, Meng-Yen Li1
1Department of Stem Cell Biology and Regenerative Medicine, Icahn School of Medicine at Mount Sinai, New York, USA.
Abstract:
Merkel cell carcinoma (MCC) is a highly aggressive neuroendocrine skin cancer with a poorly understood cell of origin and initiation process. Most MCC tumors feature monoclonal integration of Merkel cell polyomavirus DNA, which expresses viral small and large T antigens (T-Ags), responsible for driving MCC tumors. The process by which Merkel cell polyomavirus T-Ags transform cells to initiate MCC has been unclear, in part because of the lack of physiologically relevant in vivo models. Building upon our previous work, which demonstrated that SOX9-expressing hair follicle Merkel cell progenitors are susceptible to T-Ag-mediated reprogramming, we establish a mouse model in which small T-Ag expression and Trp53 attenuation in SOX9-expressing cells produce metastatic neuroendocrine tumors with histopathologic and immunophenotypic features of human MCC. Importantly, although small T-Ag alone induces partial MCC-associated gene expression, suppression of p53 is required for small T-Ag to induce neuroendocrine lineage transdifferentiation in the hair follicle. Cumulatively, these studies enhance our knowledge of MCC biology and establish a de novo MCC tumorigenesis model in a tractable immunocompetent system that will be invaluable for further advancements in the field.
Insights
Merkel cell carcinoma (MCC) initiation was modeled in mice. SOX9+ cells expressing Merkel cell polyomavirus small T antigen and lacking p53 developed metastatic neuroendocrine tumors, advancing MCC research.
Area of Science:
- Oncology
- Virology
- Dermatology
Background:
- Merkel cell carcinoma (MCC) is an aggressive skin cancer with unknown origins.
- Merkel cell polyomavirus (MCPyV) small T antigen (sT-Ag) and large T antigen (LT-Ag) drive MCC tumor development.
- Lack of in vivo models hinders understanding of MCC initiation.
Purpose of the Study:
- To establish a physiologically relevant in vivo model for MCC tumorigenesis.
- To investigate the role of MCPyV T antigens in transforming hair follicle Merkel cell progenitors.
- To elucidate the mechanisms of MCC initiation driven by viral T antigens and host factors.
Main Methods:
- Developed a mouse model expressing MCPyV sT-Ag in SOX9+ hair follicle Merkel cell progenitors.
- Utilized Trp53 attenuation in conjunction with sT-Ag expression.
- Analyzed tumor histopathology, immunophenotype, and gene expression profiles.
Main Results:
- SOX9+ cells with sT-Ag expression and Trp53 attenuation formed metastatic neuroendocrine tumors resembling human MCC.
- sT-Ag alone induced partial MCC-associated gene expression.
- p53 suppression was essential for sT-Ag-mediated neuroendocrine lineage transdifferentiation.
Conclusions:
- Established a de novo MCC tumorigenesis model in an immunocompetent system.
- Demonstrated that MCPyV sT-Ag cooperates with p53 suppression to initiate MCC.
- Provided a valuable tool for studying MCC biology and developing new therapies.
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