Histopathologic analysis of HSCR/HAEC in P18–P25 Gfra1hypo/hypomice. (A) A WT colon. (B and C) Focal epithelial ulceration, variable colon wall changes after loss of mucosal integrity, and bacterial invasion in P18–P25 Gfra1hypo/hypo mice. Marked subepithelial edema (B1, grey arrow) and basal edema (B1, green arrow) in the lamina propria, and copious edema in the submucosa (B1, red arrow). Vacuole formation, indicative of acute degenerative changes (B1 and B2, yellow arrow) and mild dilatation of crypts in the colon (B1, white arrow) also are present. Copious numbers of bacteria are attached to the surface epithelium (C1, green bold arrows). Reactive mesothelial cells (B2, green arrowheads) and thin infiltrates of eosinophils (B2, red arrowhead), neutrophils (B2, red open arrowheads), and lymphocytes in the submucosa (B2, yellow open arrowhead) are present. Focal marked epithelial damage with epithelial degeneration and necrosis (B3, black arrow) are present. Subepithelial small hemorrhage (B3, blue arrow) and infiltrating neutrophils (B3, red open arrowheads) are present. Also evident is a relative absence of AB-PAS‒positive cells (compare with panels A2 and C2 in Figure 7), which indicate goblet cell degeneration (B4).