in melanogenesis in humans, mice, and medaka. Mice affected by a condition homologous to cream exhibit irregularly shaped melanosomes, which are the organelles within melanocytes that directly produce pigment. Genes in horses such as Frame and Sabino1 produce white spotting by interrupting or limiting the migration of melanocytes from the neural crest, while the cream mutation affects the nature of the pigments produced by melanocytes. Therefore the skin, eyes, and hair of horses with the cream mutation do not lack melanocytes, melanosomes, or melanins, but rather exhibit hypomelanism. Prior to the mapping of the cream gene, this locus was titled C for "color". There are two alleles in the series: the recessive, wildtype allele C and the incomplete dominant CCr. The CCr allele represents the N153D SLC45A2 mutation. C/C recessive homozygotes are not affected by cream and have no true cream traits. C/CCr heterozygotes have one cream allele, and one wildtype non-cream allele. Only red pigment in the hair is diluted, as seen in buckskins and palominos. CCr/CCr homozygotes (homozygous creams) have no wildtype non-cream alleles. The red and black pigment in the hair are diluted to cream, the eyes are light blue and the skin is rosy pink. Cream was first formally studied by Adalsteinsson in 1974, who reported that the inheritance of palomino and buckskin coat colors in Icelandic horses followed a "semi-dominant" or incomplete dominant model. Adalsteinsson also noted that in heterozygotes, only the red pigment (pheomelanin) was diluted. The discovery that the palomino coat color was inextricably linked to the cream coat color was very significant. At one time, double dilutes, particularly cremellos, were barred from registration by many breed organizations. Cremello was thought by some to be a lethal white or albino coloring and a potential genetic defect. There also were known health implications of albinism in humans, and cultural prejudices; while a heroic figure such as Roy Rogers rode a golden palomino, the "Albino" in Mary O'Hara's Thunderhead portrayed a horse with a freakish defect. These coat colors carried vastly different cultural significance. Because the experience of breeders of palomino and buckskin horses indicated that blue-eyed cream offspring of these animals were not genetically defective, some of the research that took place nearly thirty years after Adalsteinsson's studies that identified the nature of cream dilution was directly supported by breed registries that had historically barred blue eyed creams. Cryptic creams The cream gene's preferential