Abstract
Melanocytes are pigment producing cells in the skin that give rise to cutaneous malignant melanoma, which is a highly aggressive and the deadliest form of skin cancer. Studying melanocytes in vivo is often difficult due to their small proportion in the skin and the lack of specific cell surface markers. Several genetically-engineered mouse models (GEMMs) have been created to specifically label the melanocyte compartment. These models give both spatial and temporal control over the expression of a cellular ‘beacon’ that has an added benefit of inducible expression that can be activated on demand. Two powerful models that are discussed in this review include the melanocyte-specific, tetracycline-inducible green fluorescent protein expression system (iDct-GFP), and the fluorescent ubiquitination-based cell cycle indicator (FUCCI) model that allows for the monitoring of the cell-cycle. These two systems are powerful tools in studying melanocyte and melanoma biology. We discuss their current uses and how they could be employed to help answer unresolved questions in the fields of melanocyte and melanoma biology.
Highlights
Melanocytes are the pigment-producing cells that are primarily located in skin, but are found in retinal pigment epithelium of eyes, inner ear, and some mucosal surfaces
The ideal setting to study the biology and the function of melanocytes is within its natural primary location of residence where it is exposed to the natural tissue architecture and the cellular microenvironment
We have shown that human melanomas that express cytotoxic T-lymphocyte antigen 4 (CTLA4) and other interferon-γ response genes had significant durable responses to anti-CTLA4 immunotherapy, ipilimumab [34]
Summary
Melanocytes are the pigment-producing cells that are primarily located in skin, but are found in retinal pigment epithelium of eyes, inner ear, and some mucosal surfaces. They produce melanin pigment in specialized intracellular compartments, called melanosomes, which are transferred to neighboring keratinocytes. The ideal setting to study the biology and the function of melanocytes is within its natural primary location of residence where it is exposed to the natural tissue architecture and the cellular microenvironment. Studying melanocytes in vivo has been difficult because they make up ~1% of the cellular milieu within the skin and they do not harbor reliable specific cell-surface markers that could be used to isolate them in any appreciable purity. An effective strategy in overcoming these challenges is the development of transgenic mouse models to “label” melanocytes using lineage-specific gene promoters through spatiotemporal gene regulation of a reporter construct
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