pigmentation
• after tamoxifen (4-OHT) treatment for 21 days (P28-P50) followed by shave depilation at P50 to induce the 3rd hair cycle, both pigmented and unpigmented hairs are noted at P60, whereas control mice fed a normal diet show fully pigmented hair growth
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• after 4-OHT treatment (P28-P50) followed by shave depilation at P50, some, but not all, anagen hair follicles (HFs) show a vacuolated phenotype, indicating that Cre-mediated deletion is not 100% efficient; some HFs show normal melanocyte morphology ("normal"), some HFs exhibit accumulation of cells with intracellular vesicles with some residual pigment ("intermediate"), while others show accumulation of cells with intracellular vesicles with little to no pigment ("abnormal")
• EM of skin biopsies taken at P60 show anagen hair bulbs containing melanocytes in various conditions: ~40% appear normal, another ~40% show severe vacuolization exhibiting vesicles within vacuoles resembling multivesicular bodies with very few if any melanosomes, and ~20% show an intermediate phenotype with fewer melanosomes generally of earlier stages
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• dorsal hairs from 4-OHT-treated mice accumulate ~50% less melanin relative to hairs from control mice at P85, P105, and P365
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• after 4-OHT treatment for 29 days (P21-P50) followed by shave depilation of a dorsal region at P50, mice exhibit hair greying with white hairs first seen in the depilated area at P85
• when mice are switched off tamoxifen and fed a normal chow starting at P50, more white hairs are visually apparent at P105
• numerous white hairs accumulate on the head and upper back (areas that have never been shave depilated) by P365, indicating that greying is accelerated but not induced by depilation
• greying is not progressive as mice continue to maintain the same relative level of depigmentation over the course of a year
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• after DOPA incubation, some of the multivesicular endosome-like structures observed in epidermal melanocytes of 4-OHT-treated mice contain DOPA reaction product, suggesting that TYR may be trapped within this compartment
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• after 4-OHT treatment, primary melanocytes isolated from newborn mice show a significantly reduced number of pigmented melanosomes per cell relative to vehicle-treated melanocytes
• 4-OHT-treated primary melanocytes exhibit accumulation of full length premelanosome protein (PMEL) relative to vehicle-treated melanocytes
• in culture, some 4-OHT-treated melanocytes accumulate single membrane structures resembling multivesicular endosomes with few stage IV melanosomes, while others accumulate early and late stage melanosomes with a few single membrane structures
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integument
• after tamoxifen (4-OHT) treatment for 21 days (P28-P50) followed by shave depilation at P50 to induce the 3rd hair cycle, both pigmented and unpigmented hairs are noted at P60, whereas control mice fed a normal diet show fully pigmented hair growth
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• after 4-OHT treatment (P28-P50) followed by shave depilation at P50, some, but not all, anagen hair follicles (HFs) show a vacuolated phenotype, indicating that Cre-mediated deletion is not 100% efficient; some HFs show normal melanocyte morphology ("normal"), some HFs exhibit accumulation of cells with intracellular vesicles with some residual pigment ("intermediate"), while others show accumulation of cells with intracellular vesicles with little to no pigment ("abnormal")
• EM of skin biopsies taken at P60 show anagen hair bulbs containing melanocytes in various conditions: ~40% appear normal, another ~40% show severe vacuolization exhibiting vesicles within vacuoles resembling multivesicular bodies with very few if any melanosomes, and ~20% show an intermediate phenotype with fewer melanosomes generally of earlier stages
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• dorsal hairs from 4-OHT-treated mice accumulate ~50% less melanin relative to hairs from control mice at P85, P105, and P365
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• after 4-OHT treatment for 29 days (P21-P50) followed by shave depilation of a dorsal region at P50, mice exhibit hair greying with white hairs first seen in the depilated area at P85
• when mice are switched off tamoxifen and fed a normal chow starting at P50, more white hairs are visually apparent at P105
• numerous white hairs accumulate on the head and upper back (areas that have never been shave depilated) by P365, indicating that greying is accelerated but not induced by depilation
• greying is not progressive as mice continue to maintain the same relative level of depigmentation over the course of a year
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