Expression of genes at the agouti locus and mitotic activity of the hair bulb of the mouse.

HE action of genes at the agouti locus, in combination with “wild” genes at other color loci, results in coat color phenotypes which range from all black ( a / a ) to all yellow (Ay / ) . Between these two extremes is the agouti phenotype (A/--) which is typically characterized by the presence of a subapical yellow band on an otherwise black hair. These observations indicate that alleles at the agouti locus control the nature of the pigment manufactured by melanocytes in the hair bulb, i.e., whether it is black (eumelanin) or yellow (phaeomelanin) , or whether both eumelanin and phaeomelanin will be produced (the agouti pattern). The action of the agouti gene ( A ) apparently is to control a mechanism which causes a rapid and rhythmic switch between the production of black and yellow pigment during the course of hair growth. The expression of this activity however is conditioned by the environment so that the agouti pigment pattern varies according to the integumentary environment of the hair follicle, the hair growth generation, and the hair type ( GALBRAITH 1964). Moreover, genotypically agouti melanocytes do not produce yellow pigment if they reside in hair bulbs that exceed 1 1 Op in diameter ( GALBRAITH 1969), nor do they produce yellow pigment when in extrafollicular environments (SILVERS 1957; MARKERT and SILVERS 1956). These observations indicate that the hair follicle itself plays an important role in the expression of alleles at the agouti locus. This view is supported by the work of SILVERS and RUSSELL (1955) and SILVERS (1958a, b, 1965) who have demonstrated that the melanogenic response of pigment cells is in accordance with the agouti-locus genotype of the follicle in which they reside rather than their own agouti-locus genotype. Thus the inherent capacity of the melanocyte is to produce black pigment, and phaeomelanin is produced only in the local environment of a hair follicle of appropriate agouti-locus genotype. The nature of this environment is not known, but it has been suggested that the production of yellow pigment is associated with follicular activity ( DANNEEL 1947; CLEFFMANN 1953; GALBRAITH 1964). CLEFFMANN (1963) has proposed that an elevated mitotic rate in the follicular matrix is associated with banding in agouti animals and this view would seem to be supported by the work of GALBRAITH (1964) who demonstrated that the agouti pigment pattern could be altered by the administration of the mitotic inhibitor colchicine during the period of yellow band formation.