title: Pulmonary function and pathology in hydroxypropyl-beta-cyclodextin-treated and untreated Npc1⁻/⁻ mice.
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.
authors: Dept of Pediatrics, University of Arizona, Tucson, AZ 85724, USA.
authors: Akshay
authors: A
authors: Muralidhar
authors: Ivan A
authors: IA
authors: Borbon
authors: Dyadin M
authors: DM
authors: Esharif
authors: Wangjing
authors: W
authors: Ke
authors: Rinu
authors: R
authors: Manacheril
authors: Michael
authors: M
authors: Daines
authors: Robert P
authors: RP
authors: Erickson
mesh_terms: D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000818:Animals; D002784:Cholesterol / Q000378:metabolism; D004195:Disease Models, Animal; D008168:Lung / Q000187:drug effects* / Q000473:pathology* / Q000503:physiopathology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D052556:Niemann-Pick Disease, Type C / Q000188:drug therapy* / Q000473:pathology* / Q000503:physiopathology; D012129:Respiratory Function Tests; D047392:beta-Cyclodextrins / Q000494:pharmacology* / Q000627:therapeutic use*
chemical_list: D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D002784:Cholesterol