The beta 3A subunit gene (Ap3b1) of the AP-3 adaptor complex is altered inthe mouse hypopigmentation mutant pearl, a model for Hermansky-Pudlak syndrome and night blindness

Lysosomes, melanosomes and platelet-dense granules are abnormal in the mous e hypopigmentation mutant pearl. The beta 3A subunit of the AP-3 adaptor co mplex, which likely regulates protein trafficking in the trans-Golgi networ k/endosomal compartments, was identified as a candidate for the pearl gene by a positional/candidate cloning approach. Mutations, including a large in ternal tandem duplication and a deletion, were identified in two respective pearl alleles and are predicted to abrogate function of the beta 3A protei n, Significantly lowered expression of altered beta 3A transcripts occurred in kidney of both mutant alleles, The several distinct pearl phenotypes su ggest novel functions for the AP-3 complex in mammals. These experiments al so suggest mutations in AP-3 subunits as a basis for unique forms of human Hermansky-Pudlak syndrome and congenital night blindness, for which the pea rl mouse is an appropriate animal model.