Fig. 3: Removing the DNA binding domain of TCF7L2 inhibits Wnt signaling and glutamine synthetase expression.
A To excise the DNA binding domain (DBD) of TCF7L2, specifically in the liver, LoxP sites were placed either side of exon 11, and mice homozygous for this allele were bred with Alb-Cre mice. B, C In overnight fasted 32-week-old Hep-TCF7L2ΔDBD mice, a smaller TCF7L2 protein is expressed corresponding to the excision of the DBD. The Western blot image in (B) is representative of four independent experiments on at least three liver samples harvested from both control and Hep-TCF7L2ΔDBD mice. D Tcf7l2 transcripts containing exon 11 are significantly reduced in six-week-old (42-day) mice. E, F The expression of Axin2 and Lgr5, a direct TCF7L2 transcriptional target, are similarly reduced in 6-week-old Hep-TCF7L2ΔDBD mice. G–I The expression of Ccnd1, Lef1, and Tcf7 are not different in the livers of TCF7L2 mutant mice. J In control mice, glutamine synthetase (GS) protein was found exclusively around the central vein (CV) in the liver, but GS protein was not detectable in Hep-TCF7L2ΔDBD mice. K The mRNA expression of glutamine synthetase (Glul) also was undetectable in 6-week-old Hep-TCF7L2ΔDBD mice. Sample sizes for (D–I and K): Day 0 TCF7L2LoxP/LoxP n = 5, Hep-TCF7L2ΔDBD n = 4; Day 2 TCF7L2LoxP/LoxP n = 5, Hep-TCF7L2ΔDBD n = 8; Day 5 TCF7L2LoxP/LoxP n = 5, Hep-TCF7L2ΔDBD n = 5; Day 10 TCF7L2LoxP/LoxP n = 6, Hep-TCF7L2ΔDBD n = 5; Day 15 TCF7L2LoxP/LoxP n = 6, Hep-TCF7L2ΔDBD n = 5; Day 27 TCF7L2LoxP/LoxP n = 6, Hep-TCF7L2ΔDBD n = 5; Day 42 TCF7L2LoxP/LoxP n = 6, Hep-TCF7L2ΔDBD n = 5. Data were analyzed using a two-way ANOVA and Holm-Sidak multiple comparison tests, and are presented as mean values +/− SD. Source data are provided as a Source Data file.
