Some physiological genetic aspects of mammalian melanogenesis.

During the past several years we have been studying a number of melanogenic attributes using the skins of house mice afflicted by various types of genetic damage (Foster, 1956, 1959; Foster and Thomson, 1958). Our most recent study (Foster and Thomson, 1961, and unpublished data) involves a closer scrutiny of the effects of allelic interactions at a specific locus, b (brown). Briefly, by means of a combination of manometric and turbidimetric assays we were able to measure the following major sets of attributes: (1) tyrosinase and dopa oxidase activities, (2) initially present natural melanin content, as well as newly formed melanin within incubated skin subsamples, and (3) darkening of incubation media in respirometer vessels due to escape of melanogenic intermediates from incubated skin. These assay procedures are summarized in FIGURE 1. The results most pertinent to our present discussion are summarized in TABLE 1, but it might be mentioned in passing that we were able to recognize the characteristic numerical profiles of all 10 homozygous and heterozygous genotypes involving the 4 alleles, “light” ( B L T ) , black (B) , cordovan (bc), and brown (b)-a kind of numerical “taxonomy under glass” for recognition of genotypes. Focusing attention on the comparisons of black (BB) and brown (bb) homozygotes, as well as the black heterozygote (Bb), we find that, depending upon the sets of attributes used for genotypic comparisons, we could conclude that we are dealing with (1) genetic damage when allele b is present, (2) heterotic interaction or enzymic “hybrid vigor” (luxuriance), or (3) the superiority of b over B, at least when the skin is incubated with exogenous substrates. These separate and partly incompatible conclusions obviously involve different aspects of the whole truth. One approach involves taking the reasonable position that the organism is trying to tell us it is suffering from a genetic damage when it carries a single or double dose of the brown allele (6) . This starting point is supported by the superiority of the black (BB or Bb) over brown (bb) skins with respect to the first set of pigmentary attributes listed in TABLE 1. Thus homozygous (BB) black skin has a higher natural melanin content than brown (bb) skin; it produces more melanin than does brown skin when left to its own endogenous resources (incubation in buffer) ; moreover, under conditions of substrate saturation (incubation with dopa) when brown skin seems superior to black, the total tissue-bound melanin, both initially present and newly synthesized, nevertheless is found to be greater in black skin. Thus the certain