Lung Complications in Adenosine Deaminase (ADA) Deficiency: A Mouse Model for the Human Disease

Recently, we discovered patients with inherited adenosine deaminase (ADA) deficiency are predisposed to pulmonary alveolar proteinosis (PAP). PAP is characterized by the accumulation of surfactant in the alveoli. To overcome ethical issues and limited patient samples, animal models are often utilized. Here, I investigated the lung abnormalities in ADA deficient (ADA -/-) mice, which suffer from severe hypoxia, till their death at 3 weeks. I hypothesized that, similar to ADA-deficient patients, ADA -/- mice demonstrate evidence of PAP. Indeed, electron microscopy showed thickening of type I cells, accumulation of apoptotic foamy alveolar macrophages, cholesterol and lipoproteinaceous material that is periodic-acid Schiff (PAS) positive and diagnostic of PAP. Moreover, the pulmonary abnormalities were corrected with supplementation of ADA. In conclusion, we demonstrated evidence of PAP in ADA -/- mice for the first time and their suitability to study pathogenesis of PAP in ADA deficiency.