Lung neoplasia when ATGL is absent
Upper left, normal lung morphology is seen in an H&E section from a 9 months old control mouse lung. Bronchioles are indicated by “Br”. ATGL knockout mice, where the fatal cardiac phenotype has been rescued by ATGL re-expression in the heart (Atgl-KO/cTg) develop lung neoplastic lesions when aged for 8 months and more. Upper right and lower left, a bronchiolar intraepithelial pre-neoplastic lesion (PNL), and an invasive lesion are present, respectively. Bottom right, a CK-19 IHC stained section from a 21 months old Atgl-KO/cTg lung shows a normal Br above-, and an invasive adenocarcinoma (AC) below- the dotted line.
Altered bronchiolar club cell ultrastructure
TEM images show typical stretches of bronchiolar epithelia. Atgl-KO/cTg bronchiolar epithelial club cells show fewer mitochondria (20-30 electron dense discs per club-cell cross section) as compared to the controls (40-60 per club-cell cross section). Moreover, several round, medium electron dense, lipid droplets (5-10/cellular cross section) appear in club cells from Atgl-KO/cTg mice. Lipid droplets are absent in controls.
Impaired regeneration when ATGL is absent