Constitutively active forms of RET9 but not RET51 induce cystic kidneys. Histological sections of kidneys from a +/+ mouse (A), two Hoxb7–Ret9–MEN2A Tg mice (B,C), a Hoxb7–Ret9–MEN2B mouse (D) and a Hoxb7–Ret51–MEN2A mouse, all at E18.5. The medulla (M), cortex (C), and nephrogenic zone (N) are labeled in A. (B) A severe case of cystic dysplasia caused by Hoxb7–Ret9–MEN2A. The cysts, which appear to derive from UB tips, replace much of the nephrogenic zone, and display hyperplastic features, such as stratification of the epithelium, as shown at higher magnification in F (arrows). In addition, the medulla displays abnormal branching of the collecting ducts, as shown at higher magnification in G. (C) A less severe case of cystic UB tips (arrows) in a different Hoxb7–Ret9–MEN2A founder. (H) A section for the same kidney as in C, stained with the UB-specific lectin dolichos biflorus (brown stain) (D'Agati and Trudel 1992), confirming the origin of the epithelial cysts. (D) a kidney from a Hoxb7–Ret9–MEN2B founder displays cystic UB tips in the peripheral nephrogenic zone (arrows) as well as cysts deeper in the cortex (arrowheads). (E) A bifid kidney from a Hoxb7–Ret51–MEN2A Tg mouse, with duplication of the ureter, pelvis, and renal pyramid.