Identification of novel loci associated with respiratory disease by a forward genetic approach in mouse

The objective of this research is to help elucidate the genetic causes and developmental mechanisms of respiratory disease.

A large-scale ethylnitrosourea (ENU) mutagenesis forward genetic screen is being carried out to identify regulators of lung cell differentiation, alveolar morphogenesis, pulmonary vascular development as well as tracheal cartilage ring formation. We have screened 157 C57BL/6J F1 animals for recessive phenotypes at P7, and are currently trying to recover at least 51 potential respiratory disease mouse models including emphysema, pneumonia, alveolar capillary dysplasia (ACD), idiopathic pulmonary fibrosis (IPF), pulmonary hypertension (PH), pulmonary hypoplasia, pulmonary hemorrhage, respiratory distress syndrome (RDS) and tracheomalacia.

Whole-exome sequencing is being utilized to identify the mutated genes responsible for these phenotypes, and follow-up analysis will include detailed examination of the role of these genes in lung development and disease. Due to the unbiased nature of this phenotype-driven screen, these findings are expected to uncover novel respiratory disease pathways with possible therapeutic implications.

*Presenting author