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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.
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