Figure 2. Characteristics of CDX2P-CreER^T2 Cdx2^fl/fl Braf^CA mice.

(A) Kaplan-Meier curves of CDX2P-CreER^T2 Cdx2^fl/fl Braf^CA (Cdx2^-/- Braf^V600E, n = 7), CDX2P-CreER^T2 Apc^fl/+Cdx2^fl/fl Braf^CA (Apc^+/- Cdx2^-/- Braf^V600E, n = 5), CDX2P-CreER^T2 Cdx2^fl/fl (Cdx2^-/-, n = 6), and CDX2P-CreER^T2 Braf^CA (Braf^V600E, n = 5) mice, after two daily doses of TAM (150 mg/kg). p<0.002 when comparing Cdx2^-/- or Braf^V600E to Cdx2^-/- Braf^V600E or Apc^+/- Cdx2^-/- Braf^V600E by log-rank test; p=0.158 when comparing Cdx2^-/- Braf^V600E to Apc^+/- Cdx2^-/- Braf^V600E by log-rank test. (B) Macroscopic image of the tumors at the proximal colon-cecum-ileum junction of CDX2P-CreER^T2 Cdx2^fl/fl Braf^CA mice. Left: protuberant tumor (T1) located at the proximal colon-cecum-ileum junction; Right: polypoid lesions (T2) that occupied at the entire terminal ileum to cecum region. # indicates the proximal colon; indicates the ileum. Scale bar, 10 mm (C) Histological features of the proximal colon-cecum-ileum junction tumor of CDX2P-CreER^T2Cdx2^fl/fl Braf^CA mice. Two major components were found in the tumor: serrated region (upper right) and mucin-rich region (lower left). Scale bars, 200 μm for low magnification image (left); 50 μm for high magnification images (right). (D) Serrated region showing invasion into submucosa. Dashed-line highlights muscular mucosa. Scale bar, 100 μm. See also Figure 2—source data 1 for panel A.

DOI: http://dx.doi.org/10.7554/eLife.20331.007

Figure 2—figure supplement 1. Combined Cdx2 inactivation and Braf^V600E mutation in mouse intestinal epithelium promotes the formation of tumors with serrated morphology.

H and E staining of proximal colon tissues from a wild-type mouse (A), a CDX2P-CreER^T2 Braf^CA mouse (B) and a CDX2P-CreER^T2 Cdx2^fl/fl mouse (C) after TAM injection. Scale bars, 100 μm. (D) Genotyping of Braf and Cdx2 in serrated-region and mucin-rich region in the tumor of CDX2-CreER^T2 Cdx2^fl/fl Braf^CA mutant mice using DNA samples obtained by Laser capture microdissection. Only serrated-region had Braf^V600E mutation and both regions had Cdx2 loss. (E) Representative H and E (left panels) and immunohistochemical staining for β-catenin (right panels) in a CDX2P-CreER^T2Cdx2^fl/fl Braf^CA mouse 143 days after two daily doses of TAM (upper panels) or a CDX2P-CreER^T2 Apc^fl/+Cdx2^fl/fl Braf^CA mouse 114 days after two daily doses of TAM (lower panels). Scale bars, 100 μm.

DOI: http://dx.doi.org/10.7554/eLife.20331.010