Fig. 4. Effect of ADAM17 deficiency on postnatal mammary development. (A-F) Whole mounts of paired wild-type (A-E), Adam17^–/– (A'-E') and surgically recombined (F,F') mammary glands grown under contralateral kidney capsules (A-C,F) or in surgically cleared fat pads (D,E) for 2 (A), 3 (B,D,F) or 5 (C,E) weeks with (B,C,F) or without (A,D,E) slow-release estradiol pellets. Adam17^–/– outgrowths (arrowheads) were consistently smaller than contralateral wild-type outgrowths, whereas the extent of estradiol-induced alveolar differentiation was similar in each respective host (e.g. B versus B'). (G,H) Paired Adam17^–/– transplants were also grown for 3 weeks in the presence of estradiol and adjacent AREG (a) or placebo (p) pellets. The farthest AREG pellet to yield greater-than-normal growth was 0.75 mm from the epithelium (double-headed arrow in G), whereas the closest pellet to have no effect on growth as compared to its placebo control was 1.4 mm from the epithelium (double-headed arrow in H). Scale bar: 500 µm in A'; 2 mm in D,D'; 2.5 mm in E,E'; 1 mm in all other panels and inserts. (I) Overall ductal lengths for newborn wild-type and Adam17^–/– mammary glands, 2-week-old renal transplants, and 3- and 5-week-old cleared fat pad grafts in the absence of added estradiol. Error bars at birth and 2 weeks are hidden by the mean data points. (J) Epithelial areas of paired (connected) and unpaired renal transplants with the indicated epithelial and stromal genotypes (KO, Adam17^–/–; WT, wild type). The non-recombined pairs on the left were grown for 3-6 weeks, whereas all other transplants were grown for 3 weeks in the presence of added estradiol. Bracketed data points are those for which AREG pellets were within 0.75 mm of the Adam17^–/– epithelium. (K) Mean epithelial areas of non-recombined mammary glands at various times after renal transplantation in the presence of E2.