Table 1.

Hedgehog Pathway Gene Knockout Lung Phenotypes

Genotype	Lung Phenotype	Comments	Citation
Shh−/−	Single-lobe hypoplastic lungs with decreased epithelium/mesenchyme; malformations of the trachea and trachea-esophageal fistula	Lethal at birth	93, 94
Shh+/−	No reported abnormalities	Viable	162
Ptch1−/−	Lethal before lung development begins	Lethal at E8.5–E9.5	53, 96
Ptch1+/−	No reported abnormalities	Viable	96
Gli1−/−	Normal appearing	Viable	99
Gli2−/−	Hypoplastic lungs with severe patterning defects (single lobe right lung) and diminished epithelium/mesenchyme; mildly hypoplastic trachea and esophagus	Lethal at birth	91
Gli2+/−	Normal appearing	Viable	99
Gli3−/−	Hypoplastic lungs of decreased size and abnormal shape of the lobes	Lethal around E14.5	92
Gli3+/−	Normal appearing	Viable	103
Gli1−/−; Gli2+/−	Hypoplastic lungs of decreased size, less severe than Gli1−/−; Gli2−/−	50% lethal until P21	99
Gli1−/−; Gli2−/−	Severely hypoplastic, two lobes	Lethal at birth	53, 99
Gli2−/−; Gli3+/−	Hypoplastic lungs with abnormal proximal lung development with failure to separate left and right lung and formation of a tracheobronchial fistula; distal lung partially formed	Lethal at birth	91
Gli2−/−; Gli3−/−	Most severe phenotype; fail to form trachea, lung, and esophagus	Lethal at E10.5; some embryos survive until E13.5	91
Hhip−/−	Single-lobe hypoplastic lungs with defective formation of the second generation of lung buds	Lethal at birth	38
Hhip+/−	No abnormalities reported	Viable	38
Hhip−/−; Ptch1+/−	More severe lung hypoplasia than Hhip+/− lungs; mesenchyme thickened	Lethal at birth	38

Definition of abbreviations: E, embryonic day; P, postnatal day.