In addition to the significance of the similarities between allophenic pigment patterns and those produced by a few autosomally inherited and all X-linked coat-color determinants (see Chapter 8), gene expression in allophenics also relates to the subject of white spotting. Inasmuch as it has been shown that white spotting, in contrast to albinism, results from an absence of melanocytes, it is hardly surprising that the allophenic pigment patterns which are produced when potentially white spotted and fully pigmented embryos are merged are usually quite different from the patterns which occur when blastomeres from albino and pigmented genotypes are aggregated.
In the mouse there are a number of genes [e.g., white ( Miwh), dominant spotting ( w)] which when heterozygous produce white spotting but when homozygous result in animals with no pigment in their coats at all. Such homozygotes may be considered as "one big spot" since, like the white spotted areas of pigmented mice, and unlike the situation in albinos, their hair follicles do not possess any melanocytes (clear cells) ( Silvers, 1956). When allophenics are produced from merging the embryos of such all-white animals with those of a fully pigmented strain, the never resemble the archetypal pattern of c/c <--> +/+ allophenics. Such allophenics either resemble the phenotypes of ordinary white-spotted mice or they are completely pigmented ( Mintz, 1971a). For example, when a/a;Miwh/Miwh ("one big spot") blastomeres are aggregated with A/A (pigmented) blastomeres about 50% of the allophenics which are skin mosaics, i.e., display areas of both agouti and nonagouti pigmentation, are white-spotted while the remainder are fully pigmented. In contrast, in A/A;C/C <--> a/a;c/c allophenics both pigmented and nonpigmented areas usually are present whenever hair follicle mosaicism occurs. It thus appears that for some reason Miwh/Miwh melanoblast clones are much less likely than albino melanoblast clones to lead to any phenotypic manifestation in allophenic animals. To account for this Mintz ( 1970, 1971a) proposes that the Miwh/Miwh melanoblast clones are inviable and that, depending upon when they die, they may or may not be replaced by an invasion of melanoblasts from a viable (+/+) clone. If they die early in development, the areas they occupy can usually be invaded and replaced by +/+ clones. On the other hand, if their death occurs late in development, the +/+ cells are unable to proliferate and migrate sufficiently to "fill the gaps." 5
Another factor which can influence the ability of viable clones to migrate into and pigment regions previously occupied by nonviable clones is the growth rate of the area. For example, it is less likely that a +/+ clone will be able to completely replace an inviable clone in a region which grows relatively rapidly, such as the rump, than to replace such a clone in a more slowly growing region such as the neck ( Mintz, 1970).
Still another factor which influences the amount and location of the white spotted areas is the late closure of some regions and the distal locations of others. Thus, some distal areas, such as the feet and the tip of the tail, are often white and this Mintz ( 1970) attributes to the inability of +/+ clones to reach these areas. The comparatively late closure of the umbilical region, or of the anterior neural folds, may also lead to a white belly spot or a spot on the top of the head as a consequence of viable melanoblasts not being able to migrate into these areas.
Once again all of the white spotting patterns which one finds in these allophenic animals mimic those produced in single genotype mice by known spotting genes ( Figure 7-7). This includes the fact that many white spotted genotypes are exemplified by a belly spot, by a head spot, by white feet and a white tail tip, or by a white band (belt) around the trunk (which presumably represents an inviable clone(s) which failed to be replaced). Mintz ( 1969a, 1969b) therefore suggests that white spotting results from preprogrammed clonal death, i.e., that white spotted genotypes such as Miwh/+ and W/+, like Miwh/Miwh <--> +/+ allophenics, possess some melanoblast clones which yield normal populations of functioning pigment cells and others which give rise to inviable populations of these cells, and that the spotting patterns produced by these clones are a consequence of exactly the same factors which operate in the allophenic model.
To support her contention that white spotting results from genotype-specific melanoblast cell death and that this lethality is entirely a consequence of gene expression within the melanoblasts, and not due to an influence of the skin environment, Mintz carried out the following experiment: she produced W/W <--> +/+ allophenics from animals known to bear different alleles at the major histocompatibility locus, known as the H-2 complex ( J. Klein, 1975), and then demonstrated that both the white and pigmented areas of these animals possessed cells of both H-2 types. Thus, when pieces of white skin or of pigmented skin were grafted separately from these allophenics to members of the two isogenic strains from which they were derived, in every case a semirejection occurred. This indicates clearly that despite the fact that the melanoblasts in these grafts must have been derived from only one of the strains, the skin in which they reside (and do not reside) nevertheless is comprised of cells from both ( Mintz, 1970). 6