Aberrant lung structure, composition, and function in a murine model of Hermansky-Pudlak syndrome

Am J Physiol Lung Cell Mol Physiol. 2003 Sep;285(3):L643-53. doi: 10.1152/ajplung.00024.2003. Epub 2003 May 30.


Hermansky-Pudlak syndrome (HPS) is a genetically heterogeneous inherited disease causing hypopigmentation and prolonged bleeding times. An additional serious clinical problem of HPS is the development of lung pathology, which may lead to severe lung disease and premature death. No cure for the disease exists, and previously, no animal model for the HPS lung abnormalities has been reported. A mouse model of HPS, which is homozygously recessive for both the Hps1 (pale ear) and Hps2 (pearl) genes, exhibits striking abnormalities of lung type II cells. Type II cells and lamellar bodies of this mutant are greatly enlarged, and the lamellar bodies are engorged with surfactant. Mutant lungs accumulate excessive autofluorescent pigment. The air spaces of mutant lungs contain age-related elevations of inflammatory cells and foamy macrophages. In vivo measurement of lung hysteresivity demonstrated aberrant lung function in mutant mice. All these features are similar to the lung pathology described in HPS patients. Morphometry of mutant lungs indicates a significant emphysema. These mutant mice provide a model to further investigate the lung pathology and therapy of HPS. We hypothesize that abnormal type II cell lamellar body structure/function may predict future lung pathology in HPS.

Publication types

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

MeSH terms

  • Adaptor Protein Complex 3
  • Adaptor Protein Complex beta Subunits
  • Animals
  • Bronchoalveolar Lavage Fluid / cytology
  • Bronchoalveolar Lavage Fluid / immunology
  • Disease Models, Animal
  • Female
  • Hermanski-Pudlak Syndrome / pathology*
  • Hermanski-Pudlak Syndrome / physiopathology*
  • Lung* / abnormalities
  • Lung* / pathology
  • Lung* / physiopathology
  • Male
  • Membrane Proteins / genetics
  • Membrane Transport Proteins*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Organ Size
  • Pneumonia / pathology
  • Pneumonia / physiopathology
  • Proteins / genetics
  • Pulmonary Surfactants / analysis
  • Respiratory Mechanics
  • Respiratory Mucosa / immunology
  • Respiratory Mucosa / pathology
  • Respiratory Mucosa / physiopathology


  • AP3B1 protein, human
  • Adaptor Protein Complex 3
  • Adaptor Protein Complex beta Subunits
  • Hps1 protein, mouse
  • Membrane Proteins
  • Membrane Transport Proteins
  • Proteins
  • Pulmonary Surfactants