There is no endeavor that has contributed more to our understanding of how specific coat-color determinants produce their phenotypic effects than Mintz's work on allophenic mice (see Mintz, 1967, 1970, 1971a). Indeed, because her observations on these mice are so intimately related to the mode of action of the X-linked coat-color determinants, as well as those which produce white spotting, it is necessary to review this remarkable work in some detail before considering these subjects.
Allophenic mice are produced ( Figure 7-1; for specific details see Mintz, 1971b) by explaining in vitro two cleavage-stage embryos of dissimilar genotypes and placing them in contact after their membranes are removed. Following this procedure the cells migrate in the composite mass, and a double size, genetically mosaic blastocyst develops which is transferred surgically to the uterus of a pseudopregnant mother. Normal embryo size subsequently is restored and many of the composites are viable at birth and live a "normal" life.
Because the two genotypes from which these mice are derived jointly participate in their development (and in this very important respect allophenic mice are unlike experimental radiation or other graft chimeras) they have been invaluable in investigating a wide range of questions (see Mintz, 1974), not the least of which are those involving pigmentation. Thus, when cells from embryos of two different coat-color genotypes, e.g., black ( B/B) and brown ( b/b), are combined the resultant bicolored animals display a wide range of phenotypes, spanning from those with only a small proportion of black ( B/B) to those which are almost completely of this color ( Figure 7-2). Nevertheless, these different phenotypes all represent variations on the same theme or pattern and it is precisely this pattern, the so-called archetypal or "standard pattern" ( Mintz, 1967), and its variations, which reveal the mechanisms by which most, if not all, coat-color phenotypes are produced (not only in mice but in all mammals). The "standard" or archetypal pattern of the allophenic mouse occurs when approximately equal proportions of melanoblasts of the two colored strains contribute to its phenotype and, by chance, alternate in their original positions. When this occurs in the BB <--> b/b situation an animal is produced with transverse black and brown bands of similar width, extending from the mid-dorsum to the mid-ventrum. This striping pattern is continued down the length of the head, body, and tail with the banding on one side of the mid-dorsum being completely independent from that on the other side. Mintz ( 1967) proposes that each band represents a single clone on that side, descended from one primordial melanoblast in the neural crest. Thus, inasmuch as mice displaying this standard pattern possess 17 stripes the head has three, the body six and the tail eight and those on one side of the mid-dorsum are derived independently from those on the other, she contends that the entire population of melanocytes is derived from a total of 34 clonal initiator cells ( Mintz, 1967). 1 This interpretation not only is completely in accord with the fact that the primordial melanoblasts originate in the neural crest longitudinally flanking the dorsal midline on either side, and progressively proliferate and migrate laterally towards the mid-ventrum ( Rawles, 1947), but it is also in accord with transplantation studies which have shown that the areas of different color in the coats of these mice are genotypically specific and express their mutually exclusive allelic phenotypes ( Mintz and Silvers, 1970).