32H BIOCHEMICAL GENETICS 



Although such immunologically tolerant mammals may have some utility in 

 studies concerned with mammalian pigmentation, it is doubtful whether they will ever 

 prove to be as useful as the tolerant avian embryos. This appears evident for a 

 number of reasons. Mammalian embryos cannot be manipulated experimentally as 

 can avian embryos, so that the transplantation of embryonic tissues must of necessity be 

 made to newborn or older hosts. In mammals the tolerance-responsive period, 

 determined by the genetic disparity between donor and host, usually requires exposure 

 of the fetus to homologous cells. This is certainly the case in the guinea pig and 

 appears to apply to many strain combinations in the mouse. Furthermore, in most 

 species fetal inoculations are attended by a high mortality rate. 



The availability of coisogenic color stocks and inbred lines of mice has made it 

 unnecessary to resort to the production of immunologically tolerant animals since 

 these animals offer genetically tolerant combinations for transplantation studies. The 

 existence of these stocks, therefore, not only makes it possible to perform similar trans- 

 plantation studies in mammals hitherto restricted to avian embryos but, in addition, 

 offers the experimentalist genetically uniform animals which have no parallel in any 

 avian species. 



The facility with which these animals lend themselves to transplantation studies 

 has already been utilized in a number of investigations to determine the mode of action 

 of some of the genes concerned with pigmentation or its absence. An account of some 

 of these studies, dealing with the action of genes at the agouti locus and with those 

 concerned with white spotting and albinism, follows. 



Analysis of action of the genes at the agouti locus. — The six alleles at the agouti locus of 

 the mouse determine the nature of the melanin produced by the melanocytes of the hair 

 bulbs, that is, whether it is eumelanin (black, brown), phaeomelanin (yellow), or both. 

 By substituting different alleles at this one locus the phenotype can be made to vary 

 from all black (extreme nonagouti, a e a e ) to all yellow {A y -). Between these extremes 

 are the agouti (A-), yellow-bellied agouti {A w -), black-and-tan (a 1 -) and nonagouti (aa) 

 types which exhibit varying proportions of eumelanin and phaeomelanin. The 

 agouti phenotype is characterized by a yellow banding of the otherwise black or brown 

 hairs over most of the body, that is, the main eumelanin coloration is interrupted by a 

 phaeomelanotic band ; the yellow-bellied agouti is identical with the above on its dorsum, 

 but like the black-and-tan phenotype, has a yellowish ventrum which, depending upon 

 its genetic background and regional variations, may contain either completely yellow 

 hairs or yellow hairs with dark bases. The dorsum of the nonagouti animal is similar 

 to that of the black-and-tan, containing only eumelanin pigment except in the region 

 of the ear where some yellow-containing hairs are also found. Although the ventrum 

 of the nonagouti animal is also predominantly eumelanotic, yellow pigment is found in 

 some of the hairs of certain regions, for example, around the mammae and perineum. 

 The extreme nonagouti, the last mutant described in the series, 595 is completely 

 black. 



The dominance relationships between these various alleles differ between the 



