It has long been known that lethal yellow (Ay) may significantly reduce the amount of white spotting. This was first noted by Little ( 1917a, 1917b) who observed that Ay/a;W/+;s/+ and Ay/a;W/+;s/s mice displayed much less white in their coats than the corresponding nonagouti ( a/a) genotypes. It was subsequently shown ( Dunn et al., 1937) that this was due entirely to the effect of Ay on dominant spotting ( W/+) as Ay does not appear to have any influence on the genes of the piebald group ( s and the " k" genes); nor is there any evidence that either white-bellied agouti ( Aw) or black-and-tan ( at) have any influence on these genes ( Carroll, 1934; Hughes, 1934; both quoted from Dunn et al., 1937).
In contrast to the lack of influence which Ay has on piebald ( s/s) spotting (see also Lamoreux, 1973), recessive yellow, piebald ( e/e;s/s) mice consistently showed less spotting than their black or brown piebald sibs ( Hauschka et al., 1968), and both Ay/a;s/sl and e/e;s/sl yellow animals had more pigment than a/a;E/E;s/sl mice ( Lamoreux, 1973). Indeed, Lamoreux found that lethal spotting ( ls/ls), belted ( bt/bt), splotch ( Sp/+), Jay's dominant spotting ( Wj/+), flex-tailed ( f/f), and white all produced significantly less white spotting when combined with lethal yellow (Ay) than when associated with nonagouti (a/a). 28 She also found that ls/ls and MIwi/+ (but not Sp/+) produced less spotting when combined with recessive yellow ( e/e) and Hauschka et al. ( 1968) observed that e/e also reduced the amount of white spotting produced by belted ( bt/bt) (see Table 12-4).
Since both lethal yellow and recessive yellow appear, with few exceptions, to reduce the amount of white spotting it might seem logical to conclude that ay/ and e/e for some reason are better able than a/a and E/ to support melanoblast differentiation. However, if Mintz's hypothesis is correct these genes could have what is essentially the opposite effect, i.e., the smaller spots in yellow mice could be due to the fact that Ay/ and e/e frequently cause the melanoblasts of viable clones to take their place. If this is the case it is likely that Ay produces this adverse effect on melanoblast viability via the environment while e/e probably acts within the melanoblast itself. Thus, the inverse relationship which exists between the amount of white spotting (produced by Wj/+) and the amount of yellow in the coat of viable yellow ( Avy/) mice ( Lamoreux, 1973) could be due to the fact that the melanoblasts of inviable clones do not survive as long in "yellow" as in "agouti" phenoclones.