Pheomelanin production in the epidermis from newborn agouti mice is induced by the expression of the agouti gene in the dermis

The present study was designed to clarify the role of the agouti gene in the regulation of the proliferation and differentiation of mouse epidermal melanocytes using serum-free primary culture of epidermal melanocytes from 0.5-d-old black (a/a; C57BL/10JHir) mice and congenic, agouti (A/A; C57BL/10JHir-A/A) mice. There was no significant difference in the proliferation or differentiation of melanocytes between ala and A/A mice. However, the content of pheomelanin in culture media from A/A melanocytes was increased by L-tyrosine compared with ala melanocytes. In addition, the content of the pheomelanin precursor, 5-S-cysteinyldopa, in culture media from A/A melanocytes was dramatically increased by L-tyrosine. Moreover, pheomelanin content in the epidermis from 3.5- and 5.5-d-old A/A mice was much higher than in ala mice. Analysis of the A gene using reverse transcription-polymerase chain reaction revealed that cultured keratinocytes and melanocytes do not express the A gene. Moreover, the A gene was expressed in the A/A dermis of 0.5-, 3.5- and 5.5-d-old mice, but not in the ala dermis nor in the A/A or ala epidermis. These results suggest that A/A epidermal melanoblasts are influenced by the A gene from the dermis of neonatal mice, and are capable of synthesizing pheomelanin in the culture. Pheomelanin production in the epidermis from 3.5- and 5.5-d-old A/A mice may be induced by the expression of the agouti gene in the dermis.