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Alveolarization in retinoic acid receptor-beta-deficient mice
Journal article   Open access   Peer reviewed

Alveolarization in retinoic acid receptor-beta-deficient mice

Jeanne M Snyder, Melinda Jenkins-Moore, Sheila K Jackson, Kelli L Goss, Hui-Hui Dai, Peter J Bangsund, Vincent Giguere and Stephen E McGowan
Pediatric research, Vol.57(3), pp.384-391
03/2005
DOI: 10.1203/01.PDR.0000151315.81106.D3
PMID: 15635054
url
https://doi.org/10.1203/01.PDR.0000151315.81106.D3View
Published (Version of record) Open Access

Abstract

Retinoids bind to nuclear receptors [retinoic acid receptors (RARs) and retinoid X receptors]. RARbeta, one of three isoforms of RARs (alpha, beta, and gamma), is expressed in the fetal and adult lung. We hypothesized that RARbeta plays a role in alveolarization. Using morphometric analysis, we determined that there was a significant increase in the volume density of airspace in the alveolar region of the lung at 28, 42, and 56 d postnatal age in RARbeta null mice when compared with wild-type controls. The mean cord length of the respiratory airspaces was increased in RARbeta null animals at 42 d postnatal age. Respiratory gas-exchange surface area per unit lung volume was significantly decreased in RARbeta null animals at 28, 42, and 56 d postnatal age. In addition, alveolar ducts tended to comprise a greater proportion of the lung airspaces in the RARbeta null mice. The RARbeta null mice also had impaired respiratory function when compared with wild-type control mice. There was no effect of RARbeta gene deletion on lung platelet-derived growth factor (PDGF) receptor alpha mRNA levels in postnatal lung tissue at several postnatal ages. However PDGF-A protein levels were significantly lower in the RARbeta null mice than in wild-type controls. Thus, deletion of the RARbeta gene impairs the formation of the distal airspaces during the postnatal phase of lung maturation in mice via a pathway that may involve PDGF-A.
Pulmonary Alveoli - growth & development Retinoids - metabolism Mice, Inbred C57BL Pulmonary Alveoli - physiology Male Receptors, Retinoic Acid - metabolism Random Allocation Platelet-Derived Growth Factor - genetics Receptors, Retinoic Acid - genetics Mice, Knockout Platelet-Derived Growth Factor - metabolism Animals Protein Isoforms - metabolism Female Mice Pulmonary Alveoli - anatomy & histology Protein Isoforms - genetics

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