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Updated: Sep 2, 2025
Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells
Published on: June 7, 2019
Two novel CreERT2 transgenic mouse lines to study melanocytic cells in vivo
Isabel Stüfchen1, Ruth Beckervordersandforth1, Stefan Fischer2
1Institute of Biochemistry, Friedrich-Alexander University of Erlangen-Nürnberg, Erlangen, Germany.
Abstract:
The skin of adult mammals protects from radiation, physical and chemical insults. While melanocytes and melanocyte-producing stem cells contribute to proper skin function in healthy organisms, dysfunction of these cells can lead to the generation of malignant melanoma-the deadliest type of skin cancer. Addressing cells of the melanocyte lineage in vivo represents a prerequisite for the understanding of melanoma on cellular level and the development of preventive and treatment strategies. Here, the inducible Cre-loxP-system has emerged as a promising tool to specifically target, monitor, and modulate cells in adult mice. Re-analysis of existing sequencing data sets of melanocytic cells revealed that genes with a known function in neural cells, including neural stem cells (Aldh1L1 and Nestin), are also expressed in melanocytic cells. Therefore, in this study, we explored whether the promoter activity of Nestin and Aldh1L1 can serve to target cells of the melanocyte lineage using the inducible CreERT2 -loxP-system. Using an immunohistochemical approach and different time points of analysis, we were able to map the melanocytic fate of recombined stem cells in the adult hair follicle of Nestin-CreERT2 and Aldh1L1-CreERT2 transgenic mice. Thus, we here present two new mouse models and propose their use to study and putatively modulate adult melanocytic cells in vivo.
Insights
Researchers developed new mouse models to study melanocyte stem cells. These models use Nestin and Aldh1L1 promoters with the Cre-loxP system to track and potentially modify these cells in adult mice, aiding melanoma research.
Area of Science:
- Dermatology
- Developmental Biology
- Cancer Research
Background:
- The skin's melanocytes are crucial for protection, but their dysfunction can lead to melanoma.
- Understanding melanocyte lineage in vivo is key for melanoma prevention and treatment.
- The inducible Cre-loxP system offers precise genetic targeting in adult mice.
Purpose of the Study:
- To investigate if Nestin and Aldh1L1 promoters can target melanocyte lineage cells.
- To establish new mouse models for studying adult melanocytic cells in vivo.
- To explore the potential for modulating melanocytic cells for therapeutic strategies.
Main Methods:
- Utilized the inducible CreERT2-loxP system.
- Analyzed gene expression in melanocytic cells, noting neural stem cell gene presence.
- Employed immunohistochemistry to map melanocytic fate in Nestin-CreERT2 and Aldh1L1-CreERT2 transgenic mice.
Main Results:
- Confirmed Nestin and Aldh1L1 promoter activity in targeting melanocyte lineage cells.
- Successfully mapped the melanocytic fate of recombined stem cells in adult mouse hair follicles.
- Demonstrated the utility of the developed mouse models for in vivo studies.
Conclusions:
- Nestin and Aldh1L1 promoters are effective tools for targeting the melanocyte lineage in adult mice.
- The new transgenic mouse models provide valuable platforms for melanoma research.
- These models facilitate in vivo studies and potential modulation of adult melanocytic cells.
