4.5 Article

Two novel CreERT2 transgenic mouse lines to study melanocytic cells in vivo

Journal

PIGMENT CELL & MELANOMA RESEARCH
Volume 35, Issue 6, Pages 613-621

Publisher

WILEY
DOI: 10.1111/pcmr.13061

Keywords

inducible Cre mouse line; melanocyte; melanocyte stem cell; multipotent stem cell; Nestin-CreER(T2)

Funding

  1. Projekt DEAL

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The skin of adult mammals protects against various damages, with dysfunction of melanocytes and melanocyte-producing stem cells potentially leading to melanoma. The inducible Cre-loxP-system is a promising tool for studying melanocytic cells in vivo. Genes associated with neural cells are also expressed in melanocytic cells, suggesting potential for modulating melanocytic cells using specific promoters. New mouse models were presented to study and potentially modify adult melanocytic cells in vivo.
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 CreER(T2)-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-CreER(T2) and Aldh1L1-CreER(T2) transgenic mice. Thus, we here present two new mouse models and propose their use to study and putatively modulate adult melanocytic cells in vivo.

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