Journal article
Mice Bearing Deletions of Retinoic Acid Receptors Demonstrate Reduced Lung Elastin and Alveolar Numbers
American journal of respiratory cell and molecular biology, Vol.23(2), pp.162-167
08/01/2000
DOI: 10.1165/ajrcmb.23.2.3904
PMID: 10919981
Abstract
In mammals, including rats and mice, the development of pulmonary alveolar septa is primarily limited to late gestation and the early periods of postnatal life. Before this time, the rat lung contains a relatively large supply of endogenous retinyl ester that, together with its metabolite retinoic acid, has been shown to increase elastin gene expression and the number of alveoli. We have hypothesized that mice bearing a deletion of one or more genes encoding for retinoic acid receptors (which are DNA binding proteins that alter transcription of retinoic acid-responsive genes) may demonstrate abnormalities in retoinoid-mediated alveolar formation. Our studies demonstrate that the absence of the retinoic acid receptor-gamma (RARγ) is associated with a decrease in the steady-state level of tropoelastin messenger RNA in a subpopulation of lung fibroblasts at Postnatal Day 12. RARγ gene deletion also resulted in a decrease in whole lung elastic tissue and alveolar number, and an increase in mean cord length of alveoli (L(m)) at Postnatal Day 28. The additional deletion of one retinoid X receptor (RXR)α allele resulted in a decrease in alveolar surface area and alveolar number, and an increase in L(m). These data indicate that RARγ is required for the formation of normal alveoli and alveolar elastic fibers in the mouse, and that RAR/RXR heterodimers are involved in alveolar morphogenesis.
Details
- Title: Subtitle
- Mice Bearing Deletions of Retinoic Acid Receptors Demonstrate Reduced Lung Elastin and Alveolar Numbers
- Creators
- Stephen McGowan - University of IowaSheila K. JacksonMelinda Jenkins-MooreHui-Hui DaiPierre ChambonJeanne M. Snyder
- Resource Type
- Journal article
- Publication Details
- American journal of respiratory cell and molecular biology, Vol.23(2), pp.162-167
- DOI
- 10.1165/ajrcmb.23.2.3904
- PMID
- 10919981
- ISSN
- 1044-1549
- eISSN
- 1535-4989
- Language
- English
- Date published
- 08/01/2000
- Academic Unit
- Pulmonary, Critical Care, and Occupational Medicine; Anatomy and Cell Biology; International Programs; Stead Family Department of Pediatrics; Internal Medicine
- Record Identifier
- 9984359902502771
Metrics
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