Fig. 1: Wild-type Kras deletion alters KrasG12D mutant intestinal homoeostasis.

a Schematic representing the generation of Krasfl/G12D mice: Villin Cre, Cre recombinase; ER oestrogen receptor; lox, Cre-Lox recombination site; LSL Lox-Stop-Lox cassette. Created with BioRender.com. b Number of crypts per circumference from at least 25 of the small intestine of Kras+/+, Kras+/G12D and Krasfl/G12D mice, sampled 30 days post Cre-induction (Kras+/+, n = 3, 2M,1F; Kras+/G12D, n = 4, 2M, 2F; and Krasfl/G12D, n = 5, 4M, 1F). Data are ± s.e.m. *P = 0.0286, **P = 0.0079, one-way Mann–Whitney U test. Experiments carried out on C57BL/6J background ≥ N2. c Length (cm) of small intestine (SI) and colon of Kras+/+, Kras+/G12D and Krasfl/G12D mice, sampled 30 days post Cre-induction (Kras+/+, n = 4, 3M, 1F; Kras+/G12D, n = 4, 2M, 2F; and Krasfl/G12D, n = 5, 3M, 2F). Data are mean ± s.e.m. *P = 0.0143, **P = 0.0079 one-way Mann–Whitney U test. Experiments carried out on C57BL/6J background ≥ N2. d Representative 5-bromo-2′-deoxyuridine (BrdU), Lysozyme, Alcian blue/periodic acid-Schiff (AB/PAS) and H&E staining of Kras+/+, Kras+/G12D and Krasfl/G12D mouse small intestine, sampled 30 days post Cre-induction. Scale, 100 μm. e Top: Number of BrdU-positive cells from at least 25 half-crypts in SI from (d). Data are mean ± s.e.m, (Kras+/+, n = 3, 2M, 1F; Kras+/G12D, n = 5, 3M, 2F; Krasfl/G12D n = 5, 3M, 2F), **P = 0.004, one-way Mann–Whitney U test. Middle: Number of Lysozyme-positive cells from at least 25 crypts in SI of Kras+/+, Kras+/G12D and Krasfl/G12D in SI from (d) Data are mean ± s.e.m, (Kras+/+, n = 3, 2M, 1F; Kras+/G12D, n = 6, 3M, 3F; Krasfl/G12D n = 5, 3M, 2F), **P = 0.0022, one-way Mann–Whitney U test. Bottom: Number of PAS-positive cells from at least 25 half-crypts in SI. Kras+/+, Kras+/G12D and Krasfl/G12D in SI from (d) Data are mean ± s.e.m, (Kras+/+, n = 3, 2M, 1F; Kras+/G12D, n = 6, 4M, 2F; Krasfl/G12D n = 6, 4M, 2F). **P = 0.0011, one-way Mann–Whitney U test. Experiments carried out on C57BL/6J background ≥ N2. Source data are provided as a Source Data file.