|For the bt allele:|
|bt Allele (MGI)||Gene (MGI)||All Alleles (MGI)|
This recessive mutation ( bt; chromosome 15) has been reported twice: the first time as a spontaneous mutation in the DBA stock ( Murray and Snell, 1945) and the second time as a spontaneous mutation in strain CBA/J ( Mayer and Maltby, 1964). 15
As is usually, if not always, the case the effect which bt/bt has on the amount of white spotting is greatly augmented when it is combined with other spotting genes. 16
There are two investigations ( Mayer and Maltby, 1964; Schaible, 1972) concerned with the etiology of white spotting in bt/bt mice, and, in spite of the fact that they employed very similar protocols, their results are quite different. In Mayer and Maltby's experiments small explants of ectoderm and underlying mesoderm from potentially pigmented and spotted (belted) areas of 12- to 12.5-day-old bt/bt embryos were transplanted to the coelom of the chick. Whereas grafts from potentially pigmented regions always developed pigmented hair, and in most cases melanocytes were found in the dermis of the graft between the hair follicles, as well as in the lining of the coelom of the host, grafts from the region of the belt usually displayed no hair pigment, even though numerous melanocytes occurred in the dermis (between the white hair follicles) and in the coelom of the host. Moreover, some grafts which Mayer and Maltby believe by chance had overlapped both belted and nonbelted areas, formed pigmented hairs in one region and white hairs in another. Since these observations indicate that melanoblasts migrate freely throughout all areas of the skin of bt/bt mice, even in those areas destined to form white hairs, Mayer and Maltby contend that the unpigmented hairs must result either from "a failure of melanoblasts to gain entrance into the developing follicles, or to their failure to differentiate in this environment." They therefore conclude that bt produces a specific genetic block at the level of the hair follicle. To further support this contention they cite their observation that, unlike most other spotting genes, bt does not affect the melanocyte populations of other tissues. Thus they noted that the number of melanocytes in the harderian gland, the membranous labyrinth, the choroid, the leg muscles, and the ankle skin of bt/bt mice was the same as in +/+ animals. 17
On the other hand, Schaible's transplantation experiments yielded almost diametrically opposite results, and from donors ( ae/ae;bt/bt) which had been selected from a white-belted stock. Thus, using a slightly different grafting procedure he transplanted pieces of 12- to 14-day-old embryonic bt/bt skin to the chick coelom. Some of these grafts were proportional to the full width and one-third of the dorsoventral length of the belts (assuming that the belt region of the embryos had the same location and was proportional in size to that of the adult), while others (controls) were taken from potentially pigmented regions. Although, in accord with Mayer and Maltby, Schaible found that all grafts derived from potentially pigmented areas always displayed pigmented skin and hair, and all grafts regardless of origin displayed pigment in the skin, unlike Mayer and Maltby, he also observed pigmented hairs in grafts which had originated from the belted region. Thus all seven grafts which had originated from the lumbar area of 12- and 13-day-old wide-belt donors, and two of the six 14-day-old wide belt transplants were completely pigmented.
To explain these different results Schaible suggests that perhaps the different ages of the hosts (because of the different grafting techniques, Schaible's host embryos were a day older at the start of the experiment than Mayer and Maltby's) as well as the unique genetic backgrounds of the donors were responsible. 18 He also suggests that the failure of some of his 14-day-old embryonic grafts to develop pigmented hair could have been due to the fact that the grafting procedure was not carried out until the guard hair follicles were already formed [the first hair follicles develop on the fourteenth day of gestation ( Schumann, 1960)].
Although it may seem surprising that it was the grafts from the wide-belted region of Schaible's mice rather than those from the narrower belted area of Mayer and Maltby's animals that formed pigmented hairs, the different sizes of these transplants could be responsible. Thus if one assumes that the larger lumbar region grafts which Schaible introduced into the coelom did not expand as rapidly as they would have if left in situ (or at as rapid a rate as Mayer and Maltby's smaller grafts) this could explain why melanoblasts were able to reach hair follicles in time to become incorporated into the bulb. Indeed, both Mayer and Maltby's and Schaible's observations are most readily explained in terms of Mintz's hypothesis (see Chapter 7, Section VII). Thus the pigment cells which occurred in the skin and sometimes in the hair of their recovered "belted-region" grafts could represent a secondary population which had migrated into the explanted region after the primary population (of inviable cells) had died (but before the transplants were made), a secondary population which migrated in too late to become incorporated into the hair follicles of Mayer and Maltby's transplants, but not too late to become established in the hairs of the less rapidly expanding Schaible grafts. 19 Mintz's hypothesis also readily explains why under normal conditions the belt usually occurs just posterior to the midline. Thus she would argue that bt/bt genotypes undoubtedly possess a number of inviable melanoblast clones but that most of these are replaced after they die by melanoblasts from neighboring viable clones. However, because the region just posterior to the midline of the trunk is a rapidly growing area, viable melanoblasts are unable to repopulate it completely and hence a belt is formed. 20