Alveolarization in retinoic acid receptor-beta-deficient mice

Pediatr Res. 2005 Mar;57(3):384-91. doi: 10.1203/01.PDR.0000151315.81106.D3. Epub 2005 Jan 5.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Female
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Platelet-Derived Growth Factor / genetics
  • Platelet-Derived Growth Factor / metabolism
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Pulmonary Alveoli / anatomy & histology*
  • Pulmonary Alveoli / growth & development*
  • Pulmonary Alveoli / physiology
  • Random Allocation
  • Receptors, Retinoic Acid / genetics
  • Receptors, Retinoic Acid / metabolism*
  • Retinoids / metabolism


  • Platelet-Derived Growth Factor
  • Protein Isoforms
  • Receptors, Retinoic Acid
  • Retinoids
  • platelet-derived growth factor A
  • retinoic acid receptor beta