Figure 2.

Intestine-specific knockout of Abhd5 promotes tumorigenesis and aggressiveness of tumors in Apc^Min/− mice in an autophagy-dependent manner. (A, B) Representative immunostaining images of expression of proliferation marker MKI67, apoptosis marker TUNEL, autophagy marker LC3 and SQSTM1 in the distal ilia of 100-d-old male mice with or without intestinal knockout of Abhd5. Control, Abhd5^+/+/Cre+; ABHD5 knckout, Abhd5^f/f/Cre+. (C) Western blots of LC3 and SQSTM1 in the entire small intestine of 100-d-old male mice. Control, Abhd5^+/+/Cre+; Abhd5 knockout, Abhd5^f/f/Cre+. (D) Representative images of Swiss-role H&E sections of the entire small intestine tissue of 100-d-old male and female Apc^Min/− mice. Control, Apc^Min/− Abhd5^+/+/Cre+; Abhd5 knockout, Apc^Min/− Abhd5^f/f/Cre+, the intestinal tumors were circled as shown. (E) Apc^Min/− Abhd5^+/+/Cre+ and Apc^Min/− Abhd5^f/f/Cre+ mice were intraperitoneally administered rapamycin (3 mg/kg, once daily from the age of 30 d until the age of 100 d), and the tumor number and size in the entire small intestine were statistically analyzed. (F) Apc^Min/− Abhd5^+/+/Cre+ and Apc^Min/− Abhd5^f/f/Cre+ mice were intraperitoneally administered rapamycin (3 mg/kg, once daily, from the age of 30 d until the age of 100 days), and representative H&E sections of tumors in the small intestine of control and Apc^Min/− Abhd5^f/f/Cre+ male mice at 100 d of age. (G) Apc^Min/− Abhd5^+/+/Cre+ and Apc^Min/− Abhd5^f/f/Cre+ mice were intraperitoneally administered rapamycin (3 mg/kg, once daily, from the age of 30 d until the age of 100 d), and representative immunostaining images of CDX2, a differentiation marker of intestinal epithelial cells, revealing the differentiation status of the intestinal epithelial cell of control and homozygous (Apc^Min/− Abhd5^f/f/Cre+) male mice at 100 d of age. (*, p < 0.01; **, p < 0.001; ns, no significance).