Background
Collagen XIII is a transmembrane collagen associated with neuromuscular junction development, and in humans its deficiency
Conclusions
Changes in mouse lung function appear to represent a myasthenic manifestation of collagen XIII deficiency. We suggest that respiratory muscle myasthenia is the primary cause of the breathing problems suffered by CMS19 patients in addition to skeletal deformities. Induction of collagen XIII expression in the IPF patients' lungs warrants further studies to reveal collagen XIII-dependent disease mechanisms.
Methods
We investigated the location and function of collagen XIII in the lung to understand the origin of pulmonary symptoms in human CMS19 patients. Additionally, we performed immunostainings on idiopathic pulmonary fibrosis (IPF) samples (N=5) and both normal and fibrotic mouse lung. To study whether the lack of collagen XIII predisposes to restrictive lung disease, we exposed Col13a1-modified mice to bleomycin-induced pulmonary fibrosis.
Results
Apparently normal alveolar septum sections of IPF patients' lungs stained faintly for collagen XIII, and its expression was pinpointed to the septal fibroblasts in the mouse lung. Lung capacity was increased in mice lacking collagen XIII by over 10%. In IPF samples, collagen XIII was expressed by basal epithelial cells, hyperplastic alveolar epithelial cells and stromal cells in fibrotic areas, but the development of pulmonary fibrosis was unaffected in collagen XIII-deficient mice. Conclusions: Changes in mouse lung function appear to represent a myasthenic manifestation of collagen XIII deficiency. We suggest that respiratory muscle myasthenia is the primary cause of the breathing problems suffered by CMS19 patients in addition to skeletal deformities. Induction of collagen XIII expression in the IPF patients' lungs warrants further studies to reveal collagen XIII-dependent disease mechanisms.