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

Blood. 2000 Dec 15;96(13):4227-35.


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)

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adaptor Protein Complex alpha Subunits
  • Adaptor Proteins, Vesicular Transport
  • Adenosine Diphosphate / blood
  • Animals
  • Blood Platelets / chemistry
  • Blood Platelets / pathology
  • Chromosome Mapping
  • Disease Models, Animal*
  • Eye / pathology
  • Genes
  • Genes, Recessive
  • Genetic Heterogeneity
  • Hair Color / genetics
  • Hermanski-Pudlak Syndrome / epidemiology
  • Hermanski-Pudlak Syndrome / genetics*
  • Hermanski-Pudlak Syndrome / pathology
  • Humans
  • Kidney / enzymology
  • Kidney / ultrastructure
  • Lipofuscin / metabolism
  • Liver / enzymology
  • Liver / ultrastructure
  • Lysosomes / enzymology
  • Melanosomes / pathology
  • Membrane Proteins / genetics*
  • Mice
  • Mice, Inbred C3H
  • Mice, Mutant Strains / genetics*
  • Models, Animal
  • Monomeric Clathrin Assembly Proteins*
  • Phenotype
  • Puerto Rico / epidemiology
  • Serotonin / blood
  • Skin / pathology
  • Species Specificity


  • Adaptor Protein Complex alpha Subunits
  • Adaptor Proteins, Vesicular Transport
  • HPS1 protein, human
  • Hps1 protein, mouse
  • Lipofuscin
  • Membrane Proteins
  • Monomeric Clathrin Assembly Proteins
  • clathrin assembly protein AP180
  • Serotonin
  • Adenosine Diphosphate