Structural anomalies in the peripheral lung of Mecp2 knockout mice

Abstract

Mice that have had the methyl-CpG-binding transcriptional repressor gene Mecp2 knocked out are an established model of Rett syndrome, a neurodevelopmental disorder in humans. Previous studies have indicated that Mecp2 is highly expressed not only in brain tissues, but also in the lung. This expression pattern may play a role in the findings that Rett patients suffer respiratory impairment, and respiratory failure is a common cause of death. The present study was undertaken to examine the morphology of the peripheral lung, in the Mecp21lox mouse model (Chen et al. 2001, Nat. Genet. 27:327). . Hemizygous-null and wildtype males were anesthetized: the lungs were removed rapidly, chopped and fixed by immersion, and processed for epoxide embedding. They were sectioned, and examined by light and electron microscopy. Light microscopic observation revealed that the overall architecture of the lung appeared normal. However, the type II alveolar epithelial cells were often enlarged, and appeared to contain many, large, lamellar inclusion bodies. Electron microscopic observation confirmed that these cells often contained very large lamellar bodies, some of which appeared abnormally lamellated. In addition, the mitochondria of the type II cells often appeared unusually large and sometime misshapen. Some type II cells contained glycogen deposits, and there were lipid droplets within some interstitial cells. The results suggest that type II cell development and/or function may be affected by the Mecp2-null genotype. Glycogen within type II cells, and interstitial lipid droplets suggest that the post-natal development of the peripheral lung may also be effected. This study supported by IRSA and the Brachman Hoffman Fellowship of Wellesley College.