Faculty Collaboration Database

SP-B deficiency causes respiratory failure in adult mice. Am J Physiol Lung Cell Mol Physiol 2003 Sep;285(3):L543-9

Date

03/18/2003

Pubmed ID

12639841

DOI

10.1152/ajplung.00011.2003

Scopus ID

2-s2.0-0042178357 (requires institutional sign-in at Scopus site)   151 Citations

Abstract

Targeted deletion of the surfactant protein (SP)-B locus in mice causes lethal neonatal respiratory distress. To assess the importance of SP-B for postnatal lung function, compound transgenic mice were generated in which the mouse SP-B cDNA was conditionally expressed under control of exogenous doxycycline in SP-B-/- mice. Doxycycline-regulated expression of SP-B fully corrected lung function in compound SP-B-/- mice and protected mice from respiratory failure at birth. Withdrawal of doxycycline from adult compound SP-B-/- mice resulted in decreased alveolar content of SP-B, causing respiratory failure when SP-B concentration was reduced to <25% of normal levels. Decreased SP-B was associated with low alveolar content of phosphatidylglycerol, accumulation of misprocessed SP-C proprotein in the air spaces, increased protein content in bronchoalveolar lavage fluid, and altered surfactant activity in vitro. Consistent with surfactant dysfunction, hysteresis, maximal tidal volumes, and end expiratory volumes were decreased. Reduction of alveolar SP-B content causes surfactant dysfunction and respiratory failure, indicating that SP-B is required for postnatal lung function.

Author List

Melton KR, Nesslein LL, Ikegami M, Tichelaar JW, Clark JC, Whitsett JA, Weaver TE

MESH terms used to index this publication - Major topics in bold

Age Factors
Animals
Anti-Bacterial Agents
Doxycycline
Gene Expression
Mice
Mice, Transgenic
Pulmonary Alveoli
Pulmonary Surfactant-Associated Protein B
Pulmonary Surfactant-Associated Protein C
Respiratory Insufficiency
Survival Rate