A murine model of hereditary pulmonary alveolar proteinosis caused by homozygous Csf2ra gene disruption.

ABSTRACT: Hereditary pulmonary alveolar proteinosis (hPAP) is a rare disorder caused by recessive mutations in GM-CSF receptor subunit α/β genes (CSF2RA/CSF2RB, respectively) characterized by impaired GM-CSF-dependent surfactant clearance by alveolar macrophages (AMs) resulting in alveolar surfactant accumulation and hypoxemic respiratory failure. Because hPAP is caused by CSF2RA mutations in most patients, we created an animal model of hPAP caused by Csf2ra gene disruption (Csf2ra^-/- mice) and evaluated the effects on AMs and lungs. Macrophages from Csf2ra^-/- mice were unable to bind and clear GM-CSF, did not exhibit GM-CSF signaling, and had functional defects in phagocytosis, cholesterol clearance, and surfactant cleara

SUBMITTER: Shima K 

PROVIDER: S-EPMC8917935 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature