Genetic variations in the fine structure and ontogeny of mouse melanin granules.

SYNOPSIS. Electron microscopic observations of the fine structure and ontogeny of melanin granules in various inbred strains of mice have provided new information about the origin and structure o£ these organelles. The general features of granule development, consisting of the aggregation of subunits into fibers and the cross-linking of these fibers to form a sheet-like matrix on which melanin is deposited, are shared by all but one of the genotypes examined. The formation of the matrix sheet is coincident with the deposition of melanin which begins at periodic intervals along the matrix sheet. The deposition of melanin continues until the details of the underlying matrix are obscured. The alleles at the B, C, and P loci alter the sequence of development of melanosomes in a manner suggesting that they are structural genes for different macromolecules contained in the subunits. This theory helps to integrate diverse observations on the origin of melanin granules and the genetic control of their fine structure. The effects of alleles at the D and Ln loci indicate that these loci alter the differentiation of the melanocyte by somehow altering the mechanisms controlling the location within the cell where matrix protein begins to be synthesized. The major effect of the Ru locus is to alter the time of onset of synthesis of melanin granules; thus, it may be a regulatory gene. These observations demonstrate the importance to cellular differentiation of genetic mechanisms that alter the expression of other genes by changing time and space relationships in protein synthesis. The A locus appears to act by altering the chemical environment in which the melanocyte of the hair follicle is differentiating. The effect of this alteration is on the aggregation of the matrix subunits which the melanocyte is producing. The altered aggregation leads to different enzymatic activity, and phaeomelanin is produced instead of eumelanin. Thus, the path along which a melanocyte from a hair follicle is differentiating may be altered at the level of aggregation of newly-synthesized protein, a fact which has interesting implications regarding embryonic induction.