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Updated: May 23, 2026
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Mouse Pneumonectomy Model of Compensatory Lung Growth
Published on: December 17, 2014
Compensatory lung growth in NOS3 knockout mice suggests synthase isoform redundancy
Stefan Pokall1, Arturo R Maldonado, Charles A Klanke
1Division of Pediatric General, Thoracic, and Fetal Surgery, Center for Molecular Fetal Therapy, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA. stefan.pokall@gmail.com
Summary
Nitric oxide synthase 3 (NOS3) does not impair compensatory lung growth in mice. Redundancy mechanisms involving inducible nitric oxide synthase 2 (NOS2) may compensate for NOS3 loss.
Area of Science:
- Physiology
- Molecular Biology
- Pulmonary Medicine
Background:
- Nitric oxide synthase 3 (NOS3) generates nitric oxide (NO), promoting pulmonary vasodilation via cyclic guanosine monophosphate (cGMP).
- Sildenafil's inhibition of cGMP cleavage may influence lung growth, particularly in pulmonary hypoplasia.
- Understanding NOS3's transcriptional regulation is crucial for studying compensatory lung growth (CLG).
Purpose of the Study:
- To investigate the transcriptional regulation of NOS3 during compensatory lung growth (CLG) in a mouse model.
- To compare CLG in wild-type (WT) and NOS3 knockout (NOS3-/-) mice following pneumonectomy.
Main Methods:
- Compensatory lung growth (CLG) was induced by left pneumonectomy (PNX) in adult female mice.
- Measurements included lung dry weight, DNA, and protein quantification.
- Relative quantification of nitric oxide synthase (NOS) mRNA was performed in WT and NOS3-/- mice.
Main Results:
- NOS3 knockout mice exhibited compensatory DNA increases and non-compensatory protein increases in lung tissue post-PNX.
- Inhibition of NOS with l-NAME showed a minimal 8% reduction in CLG.
- While WT lungs showed no NOS3 mRNA upregulation, NOS3-/- lungs displayed a 2.6-fold increase in inducible NOS2 (NOS2) expression.
Conclusions:
- Loss of NOS3 function alone does not impede compensatory lung growth in mice.
- Inducible NOS2 (NOS2) may play a redundant role in compensating for NOS3 deficiency during lung growth.
- These findings highlight potential alternative pathways in pulmonary vascular adaptation.
