ABCA3 inactivation in mice causes respiratory failure, loss of pulmonary surfactant, and depletion of lung phosphatidylglycerol.

ABCA3 inactivation in mice causes respiratory failure, loss of pulmonary surfactant, and depletion of lung phosphatidylglycerol. Research Abstract Details 

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ABCA3 inactivation in mice causes respiratory failure, loss of pulmonary surfactant, and depletion of lung phosphatidylglycerol. Abstract Text:

Michael L Fitzgerald,Ramnik Xavier,Kathleen J Haley,Ruth Welti,Julie L Goss,Cari E Brown,Debbie Z Zhuang,Susan A Bell,Naifang Lu,Mary McKee,Brian Seed,Mason W Freeman,

The highly branched mammalian lung relies on surfactant, a mixture of phospholipids, cholesterol, and hydrophobic proteins, to reduce intraalveolar surface tension and prevent lung collapse. Human mutations in the ABCA3 transporter have been associated with childhood respiratory disease of variable severity and onset. Here, we report the generation of Abca3 null mice, which became lethargic and cyanotic and died within 1 h of birth. Tissue blots found ABCA3 expression was highest in lung but was also detectable in other tissues, including the kidney. Gross development of kidney and lung was normal in neonatal Abca3(-/-) pups, but the mice failed to inflate their lungs, leading to death from atelectatic respiratory failure. Ultrastructural analysis of the Abca3(-/-) lungs revealed an absence of surfactant from the alveolar space and a profound loss of mature lamellar bodies, the intracellular storage organelle for surfactant. Mass spectrometry measurement of >300 phospholipids in lung tissue taken from Abca3(-/-) mice showed a dramatic reduction of phosphatidylglycerol (PG) levels as well as selective reductions in phosphatidylcholine species containing short acyl chains. These results establish a requirement of ABCA3 for lamellar body formation and pulmonary surfactant secretion and suggest a unique and critical role for the transporter in the metabolism of pulmonary PG. They also demonstrate the utility of the Abca3 null mouse as a model for a devastating human disease.

ABCA3 inactivation in mice causes respiratory failure, loss of pulmonary surfactant, and depletion of lung phosphatidylglycerol. Publishing Authors By Initials

ML Fitzgerald,R Xavier,KJ Haley,R Welti,JL Goss,CE Brown,DZ Zhuang,SA Bell,N Lu,M McKee,B Seed,MW Freeman,

For similar respiratory tract diseases: respiration disorders: respiratory insufficiency research abstracts see: respiratory tract diseases: respiration disorders: respiratory insufficiency research

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ABCA3 inactivation in mice causes respiratory failure, loss of pulmonary surfactant, and depletion of lung phosphatidylglycerol. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: Journal of lipid research

VOLUME: 48

Page Numbers: 621-32

Journal Abbreviation: J. Lipid Res.

ISSN: 0022-2275

DAY: 1

MONTH: 12

YEAR: 2006

ABCA3 inactivation in mice causes respiratory failure, loss of pulmonary surfactant, and depletion of lung phosphatidylglycerol. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 376606

ABCA3 inactivation in mice causes respiratory failure, loss of pulmonary surfactant, and depletion of lung phosphatidylglycerol. Keywords Mesh Terms:

KEYWORDS: Respiratory Insufficiency

MESH TERMS: physiopathology

Chemical & Substance for Abstract: ABCA3 inactivation in mice causes respiratory failure, loss of pulmonary surfactant, and depletion of lung phosphatidylglycerol. Information

Substance Name: Cholesterol

Registry Number: 57-88-5

Grant and Affiliation Information for ABCA3 inactivation in mice causes respiratory failure, loss of pulmonary surfactant, and depletion of lung phosphatidylglycerol.

AFFILIATION: Lipid Metabolism Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.

Country: United States

AGENCY: United States NCRR

GRANT: P20 RR-16475

ACRONYM: RR

MEDLINETA: J Lipid Res

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