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

Akshay Muralidhar; Ivan A. Borbon; Dyadin M. Esharif; Wangjing Ke; Rinu Manacheril; Michael Daines; Robert P. Erickson

doi:10.1016/j.ymgme.2011.03.001

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

Akshay Muralidhar, Ivan A. Borbon, Dyadin M. Esharif, Wangjing Ke, Rinu Manacheril, Michael Daines, Robert P. Erickson

Pediatrics

Research output: Contribution to journal › Article › peer-review

27 Scopus citations

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.

Original language	English (US)
Pages (from-to)	142-147
Number of pages	6
Journal	Molecular Genetics and Metabolism
Volume	103
Issue number	2
DOIs	https://doi.org/10.1016/j.ymgme.2011.03.001
State	Published - Jun 2011

Keywords

Foamy macrophages
Hydroxypropyl-beta-cyclodextrins
Intracellular cholesterol transport
Niemann-Pick C1
Small animal ventilator

ASJC Scopus subject areas

Endocrinology, Diabetes and Metabolism
Biochemistry
Molecular Biology
Genetics
Endocrinology

Access to Document

10.1016/j.ymgme.2011.03.001

Cite this

@article{f1860ea9d54c40cabc07dc5b4e867ffd,

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 Npc1NIH/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.",

keywords = "Foamy macrophages, Hydroxypropyl-beta-cyclodextrins, Intracellular cholesterol transport, Niemann-Pick C1, Small animal ventilator",

author = "Akshay Muralidhar and Borbon, {Ivan A.} and Esharif, {Dyadin M.} and Wangjing Ke and Rinu Manacheril and Michael Daines and Erickson, {Robert P.}",

note = "Funding Information: This work was supported by NIH 5RO1 ED000343-5 (T. Trouard, P.I.), NIH 1R56 AI083403-01A1 (M. Daines, P.I.) and the Holsclaw Family Professorship of Human Genetics and Inherited Diseases (RPE) . We thank Dr. F. John Meaney for help with statistical analyses. ",

year = "2011",

month = jun,

doi = "10.1016/j.ymgme.2011.03.001",

language = "English (US)",

volume = "103",

pages = "142--147",

journal = "Molecular Genetics and Metabolism",

issn = "1096-7192",

publisher = "Academic Press Inc.",

number = "2",

}

TY - JOUR

T1 - Pulmonary function and pathology in hydroxypropyl-beta-cyclodextin-treated and untreated Npc1-/- mice

AU - Muralidhar, Akshay

AU - Borbon, Ivan A.

AU - Esharif, Dyadin M.

AU - Ke, Wangjing

AU - Manacheril, Rinu

AU - Daines, Michael

AU - Erickson, Robert P.

N1 - Funding Information: This work was supported by NIH 5RO1 ED000343-5 (T. Trouard, P.I.), NIH 1R56 AI083403-01A1 (M. Daines, P.I.) and the Holsclaw Family Professorship of Human Genetics and Inherited Diseases (RPE) . We thank Dr. F. John Meaney for help with statistical analyses.

PY - 2011/6

Y1 - 2011/6

N2 - 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 Npc1NIH/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.

AB - 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 Npc1NIH/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.

KW - Foamy macrophages

KW - Hydroxypropyl-beta-cyclodextrins

KW - Intracellular cholesterol transport

KW - Niemann-Pick C1

KW - Small animal ventilator

UR - http://www.scopus.com/inward/record.url?scp=79956278406&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79956278406&partnerID=8YFLogxK

U2 - 10.1016/j.ymgme.2011.03.001

DO - 10.1016/j.ymgme.2011.03.001

M3 - Article

C2 - 21459030

AN - SCOPUS:79956278406

SN - 1096-7192

VL - 103

SP - 142

EP - 147

JO - Molecular Genetics and Metabolism

JF - Molecular Genetics and Metabolism

IS - 2

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this