Table 4.

Knockout mutant emphysema models.

Mouse and gene	Phenotypes	Reference
Tissue inhibitor of metalloproteinases-3 (TIMP-3)	Progressive emphysema from two weeks old with evidence of collagen degradation and increased MMP activity	[56, 57]
Surfactant protein D (SP-D)	Progressive airspace enlargement with 3 weeks of life. Increased macrophages with activated MMPs. The gene influences the response of alveolar epithelial type II cells to the injurious events	[58, 59]
Lysosomal acid lipase (LAL)	LAL is a key enzyme in the metabolic pathway of neutral lipids. Areas of alveolar destruction because of neutrophil influx, foamy macrophages, and Clara cell hypertrophy	[60, 61]
Klotho	Klotho is an “antiageing” hormone and transmembrane protein	[62]
Integrin beta-6 (Itgb6)	Inhibition of TGF-β signaling causes increased expression of MMP-12 by macrophages.	[63]
Gamma retinoic acid receptor (RARγ)	Airspace enlargement because of impaired alveolar septation	[64, 65]
Platelet-derived growth factor A (PDGF-A)	Impaired alveolar septa lake of tropoelastin expression and lack lung alveolar smooth muscle cells	[66]
Growth factor receptor 3 and 4(GFR 3-4)	Absence of secondary alveoli	[67]
Fibulin-5/DANCE	It is a secreted extracellular matrix protein that functions as a scaffold for elastin fiber assembly. The model is due to the interruption of elastin synthesis	[68, 69]
Elastin	Deficient formation of air sacs	[70]
Tumor-necrosis alpha-converting enzyme (TACE)	Disabled saccular structures	[71]
Adenosine deaminase	Increased adenosine levels impair alveolar septation and induce inflammation	[72, 73]
POD-1	Hypoplastic lungs	[74]