THE MOUSE PALE EAR (EP) MUTATION IS THE HOMOLOG OF HUMAN HERMANSKY-PUDLAK-SYNDROME

The recessive mutation at the pale ear (ep) locus on mouse chromosome 19 was found to be the homologue of human Hermansky-Pudlak syndrome (H PS), A positional cloning strategy using yeast artificial chromosomes spanning the BPS locus was used to identify the HPS gene and its murin e counterpart. These genes and their predicted proteins are highly con served at the nucleotide and amino acid levels. Sequence analysis of t he mutant Ep gene revealed the insertion of an intracisternal A partic le element in a protein-coding 3' exon, Here we demonstrate that mice with the EP mutation exhibit abnormalities similar to human HPS patien ts in melanosomes and platelet-dense granules. These results establish an animal model of HPS and will facilitate biochemical and molecular analyses of the functions of this protein in the membranes of speciali zed intracellular organelles.