mart-1-antigen and Hermanski-Pudlak-Syndrome

The muted (mu) mouse is a model for Hermansky-Pudlak Syndrome (HPS), an inherited disorder of humans causing hypopigmentation, hemorrhaging and early death due to lung abnormalities. The mu gene regulates the synthesis of specialized mammalian organelles such as melanosomes, platelet dense granules and lysosomes. Further, balance defects indicate that it controls the synthesis of otoliths of the inner ear. The mu gene has been identified by a positional/candidate approach involving large mouse interspecific backcrosses. It encodes a novel ubiquitously expressed transcript, specifying a predicted 185 amino acid protein, whose expression is abrogated in the mu allele which contains an insertion of an early transposon (ETn) retrotransposon. Expression is likewise expected to be lost in the mu( J) allele which contains a deletion of a single base pair within the coding region. The presence of structurally aberrant melanosomes within the eyes of mutant mice together with localization of the muted protein within vesicles in both the cell body and dendrites of transfected melan-a melanocytes emphasizes the role of the mu gene in vesicle trafficking. The mu gene is present only in mice and humans among analyzed genomes. As is true for several other recently identified mouse HPS genes, the mu gene is absent in lower eukaryotes. Therefore, the mu gene is a member of the novel gene set that has evolved in higher eukaryotes to regulate the synthesis/function of highly specialized subcellular organelles such as melanosomes and platelet dense granules.

Topics: Amino Acid Sequence; Animals; Antigens, Neoplasm; Choroid; Chromosomes, Artificial, Bacterial; Cytoplasmic Granules; Cytoplasmic Vesicles; Disease Models, Animal; DNA Primers; Drosophila; Drosophila Proteins; Eye Proteins; Hermanski-Pudlak Syndrome; Homeodomain Proteins; Humans; MART-1 Antigen; Melanosomes; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Molecular Sequence Data; Mutation; Neoplasm Proteins; Pigment Epithelium of Eye; Polymerase Chain Reaction; RNA, Messenger; Sequence Homology, Amino Acid