Alveolarization in retinoic acid receptor-beta-deficient mice.
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.
Snyder
Jeanne M
JM
Department of Anatomy, University of Iowa College of Medicine, Iowa City, IA 52242, USA. jeanne-snyder@uiowa.edu
Jenkins-Moore
Melinda
M
Jackson
Sheila K
SK
Goss
Kelli L
KL
Dai
Hui-Hui
HH
Bangsund
Peter J
PJ
Giguere
Vincent
V
McGowan
Stephen E
SE
D000818:Animals; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010982:Platelet-Derived Growth Factor / Q000235:genetics / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000033:anatomy & histology* / Q000254:growth & development* / Q000502:physiology; D011897:Random Allocation; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000378:metabolism*; D012176:Retinoids / Q000378:metabolism
D010982:Platelet-Derived Growth Factor; D020033:Protein Isoforms; D018168:Receptors, Retinoic Acid; D012176:Retinoids; C075278:platelet-derived growth factor A; C082925:retinoic acid receptor beta