Respiratory defects in the CrtapKO mouse model of Osteogenesis Imperfecta.

Respiratory defects in the CrtapKO mouse model of Osteogenesis Imperfecta. Am J Physiol Lung Cell Mol Physiol. 2020 Feb 05;: Authors: Dimori M, Heard-Lipsmeyer ME, Byrum SD, Mackintosh SG, Kurten RC, Carroll JL, Morello R Abstract Respiratory disease is a leading cause of mortality in patients with Osteogenesis imperfecta (OI), a connective tissue disease that causes severely reduced bone mass and is most commonly caused by dominant mutations in type I collagen genes. Previous studies proposed that impaired respiratory function in OI patients was secondary to skeletal deformities however recent evidence suggests the existence of a primary lung defect. Here, we analyzed the lung phenotype of CrtapKO mice, a mouse model of recessive OI. While we confirm changes in the lung parenchyma that are reminiscent of emphysema, we show that CrtapKO lung fibroblasts synthesize type I collagen with altered post-translation modifications consistent with those observed in bone and skin. Unrestrained whole body plethysmography showed a significant decrease in expiratory time resulting in an increased ratio of inspiratory time over expiratory time and a concomitant increase of the inspiratory duty cycle in CrtapKO compared to WT mice. Closed chest measurements using the forced oscillation technique showed increased respiratory system elastance, decreased respiratory system compliance, and increased tissue damping and elasticity in CrtapKO mice compare...
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - Category: Cytology Authors: Tags: Am J Physiol Lung Cell Mol Physiol Source Type: research