White spotting is the absence of melanocytes (pigment cells) from part or a
ll of the locations in the body where they are normally found. At least in
the case of the W (hit) locus, white spotting has been attributed to apopto
sis. In addition to the death of melanoblasts, white spotting might result
from their failure to migrate to their normal locations. These developmenta
l failures are known to be melanocyte-specific in some instances and enviro
nment-specific in others. The environment is defined as the tissues surroun
ding the melanoblast. Patterns of white spotting were examined on mice muta
nt at the piebald (s), patch (Ph), dominant spotting (W-J2) rumpwhite (Rw)
or belted (bt) loci. The dominant spotting locus has been cloned and found
to encode KIT; it has been suggested that Patch encodes the linked alpha-PD
GF receptor. Piebald encodes the endothelin beta receptor. In each case, th
e phenotypes expressed when the allele was backcrossed onto one inbred stra
in C57BL/6 (BB), were compared with phenotypes expressed when the allele wa
s backcrossed onto a different inbred strain, JU/CtLm (JU). The literature
documents genetic loci that influence the extent of the white spotted area;
we herein demonstrate that genetic loci also influence the location where
the white spot (absence of melanocytes) will occur over the body of the mou
se. Spotting occurs in a more anterior direction on JU mice that are piebal
d, patch or dominant-spotted compared with similar BE mice. The relationshi
p is reversed in rumpwhite mice, where white spotting is more anterior in t
he C57BL/6 mice than in the JU mice. The spotting pattern of belted mice wa
s not modified by the background genome. Thus, the Mendelian observations i
ndicate that several loci, which differ in JU compared with B6 mice, influe
nce the size and the location of white spots on the mouse.