TACTICS IN PIGMENT-CELL RESEARCH 327 



determined. The availability of coisogenic a l a, Ww, A y a, Mi wh Mi + , and aa stocks 

 now makes such an investigation possible, since A y aWwMi wh Mi + genotypes! exhibit 

 more pigmentation than aaWwMi wh Mi + animals on the C57BL/6 isogenic background 

 (Russell, unpublished). It would be very interesting to determine whether 

 a t aWwMi wh Mi + genotypes phenotypically resemble the corresponding aa genotype 

 on their dorsum and the corresponding A y a genotype on their ventrum, or whether 

 there is no effect or a general effect of this allele on the amount of white spotting 

 normally present in aa\VwMi wh Mi + animals. Although the former result is not 

 anticipated, its possible occurrence would certainly have to be taken into consideration 

 in explaining two of the most perplexing problems of mammalian pigmentation — the 

 etiology of white spotting and how eumelanin formation differs from phaeomelanin 

 formation. 



APPLICATIONS OF TISSUE TRANSPLANTATION IN STUDYING MAMMALIAN 

 PIGMENTATION 



Since the acceptance or rejection of a vascularized graft depends upon the presence 

 or absence in the donor tissue of genetically determined transplantation antigens that 

 are foreign to the host, it was not until inbred and coisogenic color stocks became 

 available that the technique of graft transfer could be added to the armamentarium of 

 the mammalian pigment-cell worker. Because of the accessibility of avian embryos 

 and their almost uniform acceptance of grafts of homologous or even heterologous 

 origin, at least until hatching, embryologists, ably led by Willier and his associates, 

 had been making important discoveries bearing upon the nature and origin of melano- 

 blasts, their differentiation and the physiologic factors which influence it. The work 

 did not depend upon the use of inbred animals, which were certainly not available. 

 In retrospect, in the light of the work of Billingham, Brent, and Medawar 92 and others, 

 it now seems certain that the success of these early homologous transfer experiments 

 leading to the production of transient, or even permanent, chimeras depended upon 

 the fact that early exposure of the embryos to the foreign antigens induced a state of 

 partial or complete specific nonreactivity usually referred to as immunologic tolerance. 

 These embryos never developed the ability to reject their foreign grafts. 



Application of immunologic tolerance. — Techniques are now available 91 to render 

 adult mice and other mammals tolerant of homologous tissue grafts by inoculating 

 them either directly as fetuses or intravenously at birth or shortly thereafter (that is, 

 before their immunologic mechanism of defense has become functionally mature) with 

 suspensions of living homologous cells. Such animals, when adult, may then accept 

 tissue transplants having the same genetic constitution as the perinatally inoculated 

 cells. 



f Mi wh , white, is a semidominant associated with white spotting, and inasmuch as 

 spotting genes tend to interact synergistically with each other, WwMi wh Mi + genotypes 

 may be predominantly white. 



