Genetic and genomic approaches to complex lung diseases using mouse models

Common lung diseases are likely to be multifactorial and multigenic. In addition, the lung exhibits a limited set of biological and physiological responses, so different lung diseases exhibit significant overlap in phenotype. This complexity in the development and manifestation of lung disease poses significant challenges for developing complete and accurate models of disease. Nonetheless, a layered strategy that includes in vitro and in vivo systems can offset these limitations. In vitro systems have evolved from simple organ culture to intricate procedures for cell culture that exhibit high fidelity to behavior in vivo. Similarly, in vivo systems have evolved from traditional physiology-based models in large animals and rodents to genetic modification of mice using targeted and conditional systems. Complex traits may be studied in inbred, recombinant, or congenic strains of mice, and single gene effects may be segregated naturally or experimentally. Ultimately, results from these in vitro and in vivo models identify candidate genes for further study in humans.