An experimental investigation of pattern development in lethal spotting and belted mouse embryos

Abstract

This investigation is a study of the site of gene action in producing coat spotting in two mutant mice, belted and lethal spotting. An analysis of the pigment-forming potency of skin from the two mutants was made through the use of the technique of intracoelomic grafting. Transplants from potentially pigmented regions of 12 1 2 - and 13 1 2 - day bt bt embryos produced grafts which showed extensive pigment development in the hair and dermis of the graft and in the coelomic lining of the host. Skin isolates taken from the potentially spotted area yielded grafts possessing pigment-free hair. The dermis and coelomic lining were populated by melanocytes in essentially the same number as found in the control group. Embyros used in the lethal spotting series resulted from matings of ls + mice, since ls ls mice usually die between 2 and 3 weeks of age with megacolon. Ten embryos from a group of 45 used in this series produced grafts in which at least some pigment-free hair was found. Those grafts which produced only white hair also failed to develop pigment in the dermis and in the coelomic lining. These embryos were considered to be of the ls ls genotype, and their number corresponds well to the predicted percentage. Transplants of skin from 35 embryos of this series produced grafts which contained pigmented hair only. These embryos are considered to represent ls + and +/+ genotypes. The results of the grafting series clearly indicate that melanoblasts migrate freely throughout all areas of the skin of belted mice and that the genetic block is at the level of the hair follicle. The ls gene appears to act at a different site. An examination of the pigment content of the Harderian gland, the retina and choroid of the eye, the leg musculature, ankle skin, and the membranous labyrinth of the ear was undertaken in normal and spotting mice in an attempt to clarify further the site of gene action. These results substantiate the view that bt acts specifically on the hair follicle. Pigmentation in other tissues of bt bt mice was at the normal level. In contrast to the action of bt, ls reduces the level of pigmentation in the mouse as a whole. The melanocytes in all the tissues studied in ls ls mice, with the exception of those of the retina, were greatly reduced in number or entirely absent. The occurrence of megacolon, the variable nature of the spotting, and the evidence from the descriptive and experimental studies support the hypothesis that the neural crest is abnormal in ls ls mice.