REGULATION OF LUNG DEVELOPMENT AND DISEASE

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We cloned npas3 as the mouse homolog of a Drosophila gene, trachealess, the null mutant of which completely lacks a respiratory system. 90% of our npas3-null mice die within a few hours after birth of respiratory failure, with severely emphysematous lungs. The npas3 heterozygotes (Het) live, but have varying degrees of emphysema and/or reactive airways disease. We don't know whether there are differences in the lung phenotype at different ages (i.e. worsening of emphysema with aging) or whether there is individual variability between different animals. Micro-CT scans will permit analysis of the lung tissue of individual animals at different time points. Comparison of one npas3-Het and one wild-type littermate is an important pilot experiment for the competing renewal of our grant.