Figure 2.
TEAD2-DN suppressed Nf2-deficient phenotypes in the liver. (A) Livers from wild-type, Nf2, and Nf2 TEAD2-DN mice subjected to 2 g/L Dox treatment for 7 wk starting at gestation. Note the presence of thick hamartomas (arrowheads) at the edge of the Nf2 mutant liver. Only a remnant hamartoma (arrowhead) was visible in the Nf2 TEAD2-DN liver. Bar, 1cm. (B) Similar to A except that mice were subjected to Dox treatment for 1 yr starting at birth. Note the massive overgrowth and the presence of multiple HCC (arrows) in the Nf2 mutant liver and the near-normal appearance of the Nf2 TEAD2-DN liver. Note that bile duct hamartomas, which appeared first at the edge of the Nf2 mutant liver (shown in A), have invaded deep into the liver parenchyma by 1 yr of age, giving the Nf2 mutant liver an overall pale color. Only a remnant hamartoma (arrowhead) was visible in the Nf2 TEAD2-DN liver. (C,D) H&E (C) and CK (D) staining of liver sections from B. Note the presence of deep-penetrating CK-positive bile duct hamartoma and CK-negative HCC in the Nf2 mutant liver. Also note the greatly reduced bile duct hyperplasia and the absence of HCC in the Nf2 TEAD2-DN liver. (E) Quantification of liver-to-body weight ratio for animals analyzed in A and B. (7WG) Dox treatment for 7 wk starting at gestation; (1YB) Dox treatment for 1 yr starting at birth. n ≥ 6 for each data point. In both conditions, the overgrowth of Nf2 mutant livers was significantly suppressed in Nf2 TEAD2-DN livers (P = 1 × 10−5 and 1 × 10−7, respectively).