Fig. 6. ß-catenin is increased in postnatal TgALK3QD/QD
mouse kidney tissue. (A) Immunohistochemistry of kidney tissue from control
and TgALK3QD/QD mice at P10, using rabbit anti-human
ß-catenin and HRP-conjugated anti-rabbit antibodies. Top left panels:
Hematoxylin-stained kidney tissue from control mouse demonstrates absence of
detectable ß-catenin protein in the medulla. Hematoxylin-stained kidney
tissue from TgALK3QD/QD mouse demonstrates marked
upregulation of ß-catenin expression in a subset of tubules and
epithelial cysts in the medulla. Bottom left panels: higher power view of
kidney cortex of a TgALK3QD/QD mouse. Low levels of
ß-catenin were detected. By contrast, ß-catenin levels in the
medulla of a TgALK3QD/QD mouse kidney are greatly
increased in dilated tubules (cysts). Right panel: ß-catenin expression
in whole kidney lysate was increased by 46% in TgALK3QD
(gray) versus control (white) mice, and by a further 60% in
TgALK3QD/QD (black) mice. A representative blot is shown
above. (B) Activation of ALK3 signaling increases the activity of a
ß-catenin/TCF reporter gene in vivo. ß-galactosidase activity was
assayed in the kidneys of newborn QD/QD, Tcf-gal and QD/QD;
Tcf-gal mice. Top panels demonstrate ß-gal expression in
Eosin-stained cross-sections of the entire kidney (composite image). Lower
panels demonstrate ß-gal expression in representative corresponding
tissue sections. No ß-galexpression was detected in QD/QD
kidneys. Weak expression was detected in Tcf-gal mice. By contrast,
ß-gal expression was markedly increased in QD/QD; Tcf-gal mouse
kidney, with localization in tubular epithelium. Data are mean±s.d.
from three independent experiments.