Preclinical Mouse Model of Silicosis

Silicosis is an untreatable occupational lung disease caused by chronic inhalation of crystalline silica. Cyclical release and reuptake of silica particles by macrophages and airway epithelial cells causes repeated tissue damage, characterized by widespread inflammation and progressive diffuse fibrosis. While inhalation is the main route of entry for silica particles in humans, most preclinical studies administer silica via the intratracheal route. In vivo mouse models of lung disease are valuable tools required to bridge the translational gap between in vitro cell culture and human disease. This chapter describes a mouse model of silicosis which mimics clinical features of human silicosis, as well as methods for intranasal instillation of silica and disease analysis. Lung tissue can be collected for histological assessment of silica particle distribution, inflammation, structural damage, and fibrosis in sections stained with hematoxylin and eosin or Masson's trichrome. This approach can be extended to other chronic fibrotic lung diseases where inhalation of small damaging particles such as pollutants causes irreversible disease.