Defects in the cappuccino (cno) gene on mouse chromosome 5 and human 4p cause Hermansky-Pudlak syndrome by an AP-3-independent mechanism.

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Animal, Blood-Platelets, Chromosome-Mapping, Comparative-Study, Disease-Models-Animal, Eye, Genes-Recessive, Genes-Structural, Genetic-Heterogeneity, Hair-Color, Hermanski-Pudlak-Syndrome, Human, Kidney, Lipofuscin, Liver, Lysosomes, Melanosomes, Membrane-Proteins, Mice, Mice-Inbred-C3H, Mice-Mutant-Strains, Models-Animal, Phenotype, Puerto-Rico, Serotonin, Skin, Species-Specificity, SUPPORT-NON-U-S-GOVT, SUPPORT-U-S-GOVT-P-H-S

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Blood 2000 Dec; 96(13):4227-35.


HL31698/HL/NHLBI, HL55321/HL/NHLBI, RR01183/RR/NCRR, etal


Defects in a triad of organelles (melanosomes, platelet granules, and lysosomes) result in albinism, prolonged bleeding, and lysosome abnormalities in Hermansky-Pudlak syndrome (HPS). Defects in HPS1, a protein of unknown function, and in components of the AP-3 complex cause some, but not all, cases of HPS in humans. There have been 15 inherited models of HPS described in the mouse, underscoring its marked genetic heterogeneity. Here we characterize a new spontaneous mutation in the mouse, cappuccino (cno), that maps to mouse chromosome 5 in a region conserved with human 4p15-p16. Melanosomes of cno/cno mice are immature and dramatically decreased in number in the eye and skin, resulting in severe oculocutaneous albinism. Platelet dense body contents (adenosine triphosphate, serotonin) are markedly deficient, leading to defective aggregation and prolonged bleeding. Lysosomal enzyme concentrations are significantly elevated in the kidney and liver. Genetic, immunofluorescence microscopy, and lysosomal protein trafficking studies indicate that the AP-3 complex is intact in cno/cno mice. It was concluded that the cappuccino gene encodes a product involved in an AP-3-independent mechanism critical to the biogenesis of lysosome-related organelles. (Blood. 2000;96:4227-4235)

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