Figure 7

Loss of function of Igf2r (Igf2r^I1565A/+p) shortens survival and promotes intestinal adenoma proliferation in conditional Apc^loxp/loxp. The effects of Igf2r^I1565A/+p was determined following conditional generation of intestinal adenoma. Igf2r^I1565A/+p was first combined with homozygote Apc^loxp/loxp, and an inducible intestinal Lgr5-Cre (Lgr5CreER^T2). Tamoxifen injection induced Cre recombinase (injection at 6–8 weeks of age) in these mice, with survival and intestinal adenoma formation quantified. (a) Significant shortening of survival was observed (upto day 65) for Igf2r^I1565A/+p compared to Igf2r^+m/+p (Kaplan-Meier plot, long-rank test p = 0.0468). (b) Intestinal adenoma number in the distal small intestine was significantly lower in number when comparing Igf2r^I1565A/+p to Igf2r^+m/+p (*Distal p = 0.0149), whereas in the proximal small intestine they were signgicantly greater (*Proximal p = 0.0469). The differences in colonic adenoma between genotypes were not significant. All comparisons One-way ANOVA with Fishers LSD. (Note colonic adnoma differences were borderline with an unpaired one-tailed t-test, p = 0.0423). (c) Ki-67 proliferation labelling was significantly higher (p = 0.0302) in adenoma from Igf2r^I1565A/+p compared to Igf2r^+m/+p mice (Mann Whitney, two-tailed test). (d) Adenoma diameter were not significantly different between Igf2r^I1565A/+p compared to Igf2r^+m/+p. (Two-way ANOVA). Percentage comparisons relative to total adenoma number per mouse. (e) No significant differences in the immuno-localisation of IGF2R protein were observed between Igf2r^I1565A/+p and Igf2r^+m/+p adenoma, in relation to nuclei (DAPI) and LAMP1 (endosomal compartment). Scale bar 100 μm.