Motheaten mice--an animal model with an inherited form of interstitial lung disease.

The motheaten gene represents a single recessive mutation that occurs in mice and is associated with systemic immune abnormalities. Although they have abnormalities in several organs, homozygote animals (me/me) die by 8 wk of age from a diffuse, noninfectious lung disease. To evaluate this genetically determined model of interstitial lung disease, the lungs of these animals were studied by light and transmission electron microscopy and by bronchoalveolar lavage. Two control groups of mice were evaluated: (1) littermate normal mice, including mice without the motheaten gene (+/+) and mice heterozygous (me/+) the motheaten gene, and (2) nonlittermate normal mice (+/+). While the lungs of both control groups were normal morphologically, the lung disease in the homozygous motheaten mice progressed through 3 stages: (1) focal intra-alveolar hemorrhage with accumulations of alveolar macrophages and neutrophils in the lower respiratory tract; (2) persistent alveolitis and hemorrhage, and reparative processes including frequent mitoses of fibroblasts and type II alveolar epithelial cells; and (3) consolidation of the alveolar structures by massive accumulation of macrophages and marked derangement and fibrosis of the alveolar walls. Consistent with the morphologic findings, evaluation of mid-stage lung disease by lavage demonstrated that the alveolitis was characterized by a marked expansion of the total number of effector cells, an accumulation of neutrophils, and a marked expansion of the total numbers of T-lymphocytes and B-lymphocytes. Thus, the motheaten mouse can be regarded as a genetically determined model of interstitial lung disease characterized by alveolar hemorrhage, derangement of parenchymal cells, fibrosis, and an alveolitis with distinctive features.(ABSTRACT TRUNCATED AT 250 WORDS)