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 system of epidermal melanocytes from 0.5-day-old black (a/a; C57BL/10JHir) mice and its congenic, agouti (A/A; C57BL/10JHir-A/A) mice. There was no significant difference in the proliferation and differentiation of melanocytes between a/a and A/A mice. However, content of pheomelanin in culture media from A/A melanocytes was increased by L-tyrosine compared with a/a melanocytes. In addition, content of 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-day-old A/A mice was much higher than a/a mice. The analysis using reverse transcrition-polymerase chain reaction of the A gene revealed that cultured keratinocytes and melanocytes did not express the A gene. Moreover, the A gene was expressed in the A/A dermis of 0.5-, 3.5- and 5.5-day-old mice, but not in the a/a dermis as well as in the A/A and a/a 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-day-old A/A mice may be induced by the expression of the agouti gene in the dermis