Coat color dilution in mice because of inactivation of the melanoma antigen MART-1.

Melanoma antigen recognized by T cells 1 (MART-1) is a melanoma-specific antigen, which has been thoroughly studied in the context of immunotherapy against malignant melanoma and which is found only in the pigment cell lineage. However, its exact function and involvement in pigmentation is not clearly understood. Melanoma antigen recognized by T cells 1 has been shown to interact with the melanosomal proteins Pmel17 and OA1. To understand the function of MART-1 in pigmentation, we developed a new knockout mouse model. Mice deficient in MART-1 are viable, but loss of MART-1 leads to a coat color phenotype, with a reduction in total melanin content of the skin and hair. Lack of MART-1 did not affect localization of melanocyte-specific proteins nor maturation of Pmel17. Melanosomes of hair follicle melanocytes in MART-1 knockout mice displayed morphological abnormalities, which were exclusive to stage III and IV melanosomes. In conclusion, our results suggest that MART-1 is a pigmentation gene that is required for melanosome biogenesis and/or maintenance

Pathology and Ultrastructural Characteristics of a Hypomelanotic Variant of Transplantable Hamster Melanoma With Elevated Tyrosinase Activity

A spontaneous, hypomelanotic variant (MI) of the highly melanotic transplantable hamster melanoma of Bomirski (Ma) is the subject of this report. Tyrosinase activity is 2-3 times higher, but melanin content significantly lower than in the parental Ma melanotic melanoma. Acid phosphatase activity is similar in both, but β-glucuronidase and aryl-sulfatase A are 2-3 times higher in the hypomelanotic variant.Transplanted MI melanomas grow more slowly than the parental tumor, but metastasize with similar incidence and localization. Hypomelanotic variant melanoma cells, even those in grossly nonnecrotic parts of the transplants, show signs of low viability like swelling of the cytoplasm or cellular condensation, and disintegration. Autophagic vacuoles are numerous. They appear to be formed by enclosure of a portion of cytoplasm by cisternae of smooth endoplasmic reticulum or trans-Golgi network. These limiting cisternae contain tyrosinase as evidenced by deposition of electron dense reaction product on incubation with tyrosine or DOPA. Other sites of ultrastructural tyrosinase reaction are melanosomes and the smooth-surfaced cisternae and vesicles of the trans-Golgi network.We postulate that low cell viability, associated with autophagosome formation, is the cause for the growth retardation of the MI variant, and that the lower melanin content of these tyrosinase-rich cells is due to sequestration of a substantial portion of newly synthesized enzyme into autophagic vacuoles before it has the chance of being incorporated into melanosomes

Hypothesis: possible role for the melatonin receptor in vitiligo: discussion paper

A new unifying hypothesis for the aetiology of vitiligo is proposed, in which we postulate that the final destruction of melanocytes in vitiligo results from a cascade of reactions initiated by a disregulation of melanogenesis, caused by activation of the melatonin receptor. These events result in the high and uncontrolled production of free radicals and toxic products of melanogenesis which sequentially damage or destroy melanocytes and keratinocytes, provoke an autoimmune response against exposed intracellular or altered cell surface antigens, and increase the propensity of melanocytes to undergo malignant transformation

Hypothesis: possible role for the melatonin receptor in vitiligo: discussion paper.

A new unifying hypothesis for the aetiology of vitiligo is proposed, in which we postulate that the final destruction of melanocytes in vitiligo results from a cascade of reactions initiated by a disregulation of melanogenesis, caused by activation of the melatonin receptor. These events result in the high and uncontrolled production of free radicals and toxic products of melanogenesis which sequentially damage or destroy melanocytes and keratinocytes, provoke an autoimmune response against exposed intracellular or altered cell surface antigens, and increase the propensity of melanocytes to undergo malignant transformation