Pulmonary function and pathology in hydroxypropyl-beta-cyclodextin-treated and untreated Npc1⁻/⁻ mice

Mol Genet Metab. 2011 Jun;103(2):142-7. doi: 10.1016/j.ymgme.2011.03.001. Epub 2011 Mar 5.

Abstract

Lung dysfunction is an important part of the pathology of the neurodegenerative disorder, Niemann-Pick C1 (NPC1). We have studied the pulmonary disease in the Npc1(NIH/NIH) mouse model. On histology, we find large numbers of alveolar foamy macrophages but no alveolar proteinosis. Lung weight as percent of body weight was markedly increased; using the flexiVent small animal ventilator (SCIREQ, Inc.), we find inspiratory capacity, elastance and hysterisivity to be increased while resistance was not changed. Cholesterol measurements show a doubling of lung cholesterol levels. Collagen is also increased. Treatment of Npc1(-/-) mice with hydroxypropyl-β-cyclodextrin (HPBCD), despite efficacious effects in brain and liver, results in little difference from age-matched controls (using a CNS-expressed transgene to extend the life expectancy of the Npc1(-/-) mice) for these variables.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2-Hydroxypropyl-beta-cyclodextrin
  • Animals
  • Cholesterol / metabolism
  • Disease Models, Animal*
  • Lung / drug effects*
  • Lung / pathology*
  • Lung / physiopathology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Niemann-Pick Disease, Type C / drug therapy*
  • Niemann-Pick Disease, Type C / pathology*
  • Niemann-Pick Disease, Type C / physiopathology
  • Respiratory Function Tests
  • beta-Cyclodextrins / pharmacology*
  • beta-Cyclodextrins / therapeutic use*

Substances

  • beta-Cyclodextrins
  • 2-Hydroxypropyl-beta-cyclodextrin
  • Cholesterol