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Fig. 4. Urogenital abnormalities in Ret^DN/+ mice. (A, top row). Compared with wild-type (wt) mice, Ret^DN/+ mice showed a spectrum of renal defects, including bilateral small kidneys and unilateral renal agenesis (k, kidney; a, adrenal; ub, urinary bladder, t, testis; o, ovary; adrenal gland, arrowhead). (A, bottom row) Bar graph shows the decreased total number of glomeruli in Ret^DN/+ kidney at birth (n=3 animals, 5 kidneys), when compared with wild-type litter mates (n=3 animals, 6 kidneys) (^*=P<0.001, mean±s.e.m.). HE-stained sections show tubulocystic degeneration (arrows) in approximately 50% of 3- to 4-week-old Ret^DN/+ mice (6 out of 12) (co, cortex; me, medulla; pe, pelvis). Scale bar: 5 mm in top row; 600 µm in bottom row. (B) HE-stained sections show atrophic, degenerating seminiferous tubules with multinucleated giant cells (arrows) in Ret^DN/+ mice (P28). Wild-type (wt), Ret^9/+, Ret^TGM/+ and Ret^DNneo/+ mice show age-appropriate germ cell maturation. Scale bar: 100 µm for wild-type and Ret^DN/+ mice; 130 µm for Ret^9/+, Ret^TGM/+ and Ret^DNneo/+ mice. (C) At P28, a significant decrease in the percentage of Ret^DN/+ seminiferous tubules containing round spermatids is noted, and no tubules contain elongated spermatids (n=3 for each genotype, ^*=P<0.01, mean±s.e.m.).

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