Glucocorticoid receptor disruption delays structural maturation in the lungs of newborn mice.
Pediatr Pulmonol
; 43(2): 125-33, 2008 Feb.
Article
in En
| MEDLINE
| ID: mdl-18085690
ABSTRACT
In order to better understand the regulation of lung maturation by glucocorticoid-glucocorticoid receptor signaling, we studied glucocorticoid receptor (GR) hypomorphic mice with a mixed C57Bl6/129 sv background, in which disruption of exon 2 of the GR gene produces an N-terminal truncated GR protein. Four groups of mice were compared homozygous mice that die at birth (non-survivors), homozygous mice that survive the neonatal period (survivors), heterozygotes and wild-type mice. Newborn non-survivors had 50% thicker airspace walls and a 46% decrease in the formation of secondary crests (the beginning of alveolar secondary septation) compared to either survivor or wild-type littermates (n = 9 mice in each group). The lung tissue to airspace ratio in homozygous mice not expressing wild-type GR (non-survivor and survivor) was increased compared to heterozygotes and wild-type mice that do express wild-type GR (0.91 +/- 0.08 vs. 0.49 +/- 0.02, n = 4 in each of the four subgroups), suggesting that complete morphological maturation of the lung is dependent on effective glucocorticoid signaling through a fully functional GR. Moreover, the relatively mature lung morphology of survivor versus non-survivor newborns suggests that a partial reduction in mesenchymal thickness is compatible with capillary remodeling, alveolar septation, and viable respiratory function after birth. Our findings suggest that in mice homozygous for disrupted GR, the severity of newborn respiratory insufficiency correlates with the degree of lung structural immaturity.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Respiratory Insufficiency
/
Receptors, Glucocorticoid
/
Glucocorticoids
/
Lung
Limits:
Animals
Language:
En
Journal:
Pediatr Pulmonol
Journal subject:
PEDIATRIA
Year:
2008
Document type:
Article
Affiliation country:
Canada