Among the genes knocked out, foxf1 and TCF21 levels were reduced in the lungs of the triple n/i/eNOSs−/− mice, suggesting that the reduced foxf1 and TCF21 levels were possibly involved in the development of spontaneous pulmonary emphysema in the triple n/i/eNOSs−/− mice. This evidence concerns the gene TCF21 and pulmonary emphysema.