Uterine response to estrogen stimulation in F2 animals. (1) The ratio of uterine wet weight (milligrams) to body weight (grams) was calculated. The increase between E2-treated homozygotes (−/−) and olive oil-treated homozygotes (−/−) is lower than the increase between E2-treated wild-type mice (+/+) and olive oil-treated wild-type mice (+/+) by an average of 26%. Olive oil was used as solvent control. The t test shows a significant difference (P < 0.05) in E2-treated wild-type mice (+/+) (n = 11) and E2-treated homozygotes (−/−) (n = 11). (2, 3) The ratio of uterine water imbibition and dry weight (milligrams) to body weight (grams) was calculated. The increase between E2-treated homozygotes (−/−) and olive oil-treated homozygotes (−/−) is lower than the increase between E2-treated wild-type mice (+/+) and olive oil-treated wild-type mice (+/+) by 54% in water imbibition (2) and by 22% in dry weight (3), respectively. Olive oil was used as solvent control. The t test shows a significant difference (P < 0.05) between E2-treated wild-type mice (+/+) (n = 6) and E2-treated homozygotes (−/−) (n = 6) in both water imbibition (2) and dry weight (3). (4) Histological analysis in the uterus of F2 animals after estrogen injection. The uterus from ovariectomized F2 animals with E2 (20 μg/kg/day) was collected and quickly frozen. Each horizontal section was stained by hematoxylin and eosin and was examined histologically. A, B, and C represent wild-type mice (+/+), D, E, and F heterozygotes (+/−), and G, H, and I homozygotes (−/−). The portion of the interstitium (×25) is shown in A, D, and G, that of the epithelium in B, E, and H (×25) and C, F, and I (×50). The decreased extent of water imbibition into the interstitium (G) and of hyperplasia in epithelial cells (H and I) is shown clearly in the uterus of E2-treated homozygote (−/−). ep, epithelium; st, stroma; my, myometrium; pe, perimetrium. [Bars = 100 μm (C, F, and I) and 200 μm (A, B, D, E, G, and H).]