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(The FASEB Journal. 2007;21:939.5)
© 2007 FASEB
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939.5

Relationship between lung architecture and lung function are genetically determined

Ewa M Galdzicka, Eric D Abston, John M Bishai, Kewu Huang, Vikas Misra, Sathyavathi Muninarayana, Richard T Rabold, Wayne Mitzner and Clarke G Tankersley

Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe Street, Baltimore, MD, 21205

ABSTRACT

Genetic determinants direct various developmental aspects of lung architecture. We tested the hypothesis that lung function is associated with variation in alveoli size. To this end, F2 mice were derived from two different breeding strategies utilizing C3H/HeJ (C3) and C57Bl/6J (B6) progenitors and their recombinant inbred offspring (BXH RI strains). Quasi-static pressure-volume (PV) curves, and measurements of respiratory system impedance and metabolism were performed. Histological sections were obtained from lung tissue and quantified by determining mean chord length (MCL). The F2 mice were divided into two sub-groups based on breeding strategy (i.e. C3-like and B6-like phenotypes) and were evaluated by cosegregation analysis. The B6-like phenotype for MCL was found to cosegregate with many breathing characteristics. For example, MCL correlates with inspiratory time at baseline (r = 0.45; p<0.01) and with tissue damping (r = 0.51; p<0.05). Fewer significant associations were found using the C3-like phenotype; one unique example is the association between MCL and quasi-static compliance (r = 0.44; p<0.05). In summary, the B6-like phenotype is characterized by a significantly (p=0.05) lower MCL distribution compared to the C3-like phenotype. Furthermore, robust genetic factors that regulate variable alveolar dimensions influence lung function and mechanics.

NIA AG-21057 and NHLBI HL-010342





This Article
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Right arrow Articles by Tankersley, C. G