Histocompatibility antigen changes associated with pink-eyed dilute (p) mutations

The tight linkage between the H-4 histocompatibility locus and the pink-eyed dilute (p) locus raises the possibility that a single gene is responsible for both a histocompatibility antigen and coat color phenotype. To examine this possibility, we have investigated the effects of a spontaneous coat color mutation, pink-eyed unstable (p^un), which occurred at the p locus in the C57BL/6J inbred strain, on histocompatibility antigen phenotype. Skin grafts were transplanted from two independently maintained B6 p^un substrains to coisogenic, wild-type C57BL/6 recipients; graft rejection uniformly commenced at 6-7 weeks but did not culminate in complete graft destruction as observed in other cases of "crisis" rejection. Neither the onset of rejection time nor the intensity of rejection could be accelerated by introducing new H-2 haplotypes into the wild-type recipients. These results suggested that the p^un allele was associated with a histocompatibility antigen not shared with C57BL/6. The p^un allele is characterized by a relatively high frequency of reversion to wild-type. Therefore, skin grafts from B6-p^un donors were transplanted to homozygous, revertant (+/+) recipients which were subline-matched with the donors; these grafts underwent crisis rejection with the same time of onset of rejection as observed with C57BL/6 recipients. These observations indicate that a new histocompatibility antigen is associated with the p^un mutation and is lost upon reversion to wild type; this association is the first demonstration of a link between histocompatibility and coat color phenotypes.